Sintilimab Pharmacovigilance in Real-World Practice: Analysis Utilizing the WHO VigiAccess Database

Sintilimab Pharmacovigilance in Real-World Practice: Analysis Utilizing the WHO VigiAccess Database | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Sintilimab Pharmacovigilance in Real-World Practice: Analysis Utilizing the WHO VigiAccess Database Youjia Guo, Li Wen, Fangcheng Jiang, Liling Pan, Lei He, Zhaoji Liu, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7907424/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Sintilimab, a high-affinity PD-1 inhibitor, blocks the interaction between PD-1 and PD-L1 to restore T-cell function. Clinically used with chemotherapy for cancers like non-small cell lung carcinoma and hepatocellular carcinoma, its adverse event (AE) profile remains critical. Here we conducted the pharmacovigilance analysis of sintilimab-associated AEs using the WHO VigiAccess database. Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) were used to detect the risk signals, characterizing AE distribution at System Organ Class (SOC) and Preferred Term (PT) levels. Our analysis reveals hematologic toxicity as the predominant SOC-level AE. At the PT level, myelosuppression was the most frequently reported event. To our knowledge, these findings provide the first evidence from real-world global safety data on sintilimab’s AEs, and may enhance clinical monitoring and risk mitigation strategies for sintilimab therapy. Sintilimab adverse event real‑world pharmacovigilance study WHO-VigiAccess database Figures Figure 1 Introduction Sintilimab, a human immunoglobulin G4 (IgG4) monoclonal antibody, selectively binds programmed cell death protein 1 (PD-1) on T-cell surfaces to block the PD-1/programmed death-ligand 1 (PD-L1) pathway, thereby restoring lymphocyte-mediated antitumor activity for therapeutic efficacy in tumors 1 . Recently, sintilimab has been approved for the therapy of several solid malignancies, including non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), and classical Hodgkin's lymphoma. Among these, NSCLC and HCC remain the leading cause of global cancer mortality, posing a significant public health challenge 2 , 3 . NSCLC represents the predominant histological subtype of lung cancer. In Asian populations, approximately half of NSCLC patients carry epidermal growth factor receptor (EGFR) mutations, for which EGFR tyrosine kinase inhibitors (TKIs) serve as the standard first-line therapy 4 . For those without detectable driver mutations, immune checkpoint inhibitors (ICIs), including sintilimab, have emerged as foundational treatments for advanced NSCLC 5 . Previous study has demonstrated that sintilimab significantly improved the prognosis of patients with previously treated locally advanced or metastatic squamous-cell NSCLC 6 . Furthermore, a randomized, double-blind, phase III clinical trial showed that sintilimab combined with chemotherapy or other modalities prolonged the progression-free survival and overall survival of patients with NSCLC without EGFR or ALK mutation compared with chemotherapy alone 7 , 8 . Evidence also supports combining PD-1 inhibitors with VEGF-targeted agents or local therapies such as radiotherapy and cryoablation to overcome TKI resistance 4 , 9 – 12 . HCC is the most common form of liver cancer. In the first-line therapies of advanced HCC, the combination of sintilimab and IBI305 (a bevacizumab biosimilar) achieved a European Society for Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS) score of 5, indicating a significant clinical benefit 13 . This regimen demonstrated significant improvement in overall survival and progression-free survival benefits compared to sorafenib in Chinese patients with unresectable hepatitis B virus-related HCC in China, alongside an acceptable safety profile 14 . In summary, sintilimab demonstrates a wide range of clinical applicability, with numerous studies affirming its significant therapeutic efficacy. However, meta-analyses studies indicate that treatment intensification, whether through immunotherapy or anti-angiogenic agents, or combination regimens, elevates toxicity risks and is associated with higher adverse event (AE) rates 5 , 15 . Even single treatment with PD-1 inhibitors results in AEs. Notabley, sintilimab is associated with a higher incidence of rash compared to pembrolizumab 16 17 . To date, Sintilima’s distinct AE profile remains incompletely characterized in real-world settings and further prospective pharmacovigilance studies are needed to delineate its distinct safety spectrum. WHO-VigiAccess synthesized the reports of AEs from various countries and regions, as a real-world data warehouse of AEs, providing a global perspective of drug safety information 18 , 19 . This pharmacovigilance study addresses this gap by analyzing sintilimab-associated AEs reported in the WHO VigiAccess database from 2020–2024, predominantly across Asian populations, to inform safer clinical application. Results Basic characteristic of AEs-related patients. Table 1 summarizes cohort demographics.​​ Males predominated (64.07%), while females comprised 35.73% of cases. In terms of age distribution, patients aged ≥ 45 years constituted the majority (92.7% total), most notably those aged 45–64 years (46.61%). The cohort of 486 patients was predominantly Asian (99.79%), with reports concentrated in 2020 (30.80%) and 2021 (68.99%). Table 1 The basic demographic data related to adverse events. Characteristics Case number (Proportion, %) Gender Female 174(35.73) Male 312(64.07) Unknown 1(0.21) Age 2–11 years 1(0.21) 18–44 years 44(9.03) 45–64 years 227(46.61) 65–74 years 151(31.01) 75 years 60(12.32) Unknown 4(0.82) Region America 1(0.21) Asia 486(99.79) Reporting year 2020 150(30.8) 2021 336(68.99) 2024 1(0.21) Distribution of AEs in system organs class (SOC). Primary AE distributions appear in Fig. 1 . Specifically, the distribution of positive signals of sintilimab-related AEs at the level of systemic organ classification are described in Table 2 . According to the cumulative number of AEs cases in SOC, the top 5 SOCs are blood and lymphatic system disorders (SOC code: 10005329, n = 152), skin and subcutaneous tissuedisorders (SOC code: 10040785, n = 135), investigations (SOC code: 10022891, n = 112), general disorders and administration site conditions (SOC code: 10018065, n = 79), and gastrointestinal disorders (SOC code: 10017947, n = 65). According to the positive PT number of AEs in SOC (Table 3 ), the top 5 SOC are blood and lymphatic system disorders (SOC code: 10005329, n = 143), skin and subcutaneous tissue disorders (SOC code: 10040785, n = 99), investigations (SOC code: 10022891, n = 95), hepatobiliary disorders (SOC code: 10019805, n = 52), and endocrine disorders (SOC code: 10014698, n = 33). Table 2 Distribution of sintilimab related adverse events in different system organs class (SOC) SOC Case number, n proportion, % Positive signal number, n proportion, % Blood and lymphatic system disorders 152 18.63 6 14.63 Skin and subcutaneous tissue disorders 135 16.54 6 14.63 Investigations 112 13.73 9 21.95 General disorders and administration site conditions 79 9.68 2 4.88 Gastrointestinal disorders 65 7.97 2 4.88 Hepatobiliary disorders 58 7.11 4 9.76 Endocrine disorders 38 4.66 4 9.76 Cardiac disorders 35 4.29 2 4.88 Respiratory, thoracic and mediastinal disorders 34 4.17 1 2.44 Infections and infestations 21 2.57 2 4.88 Nervous system disorders 16 1.96 1 2.44 Renal and urinary disorders 14 1.72 1 2.44 Metabolism and nutrition disorders 12 1.47 0 0.00 Immune system disorders 11 1.35 1 2.44 Vascular disorders 11 1.35 0 0.00 Musculoskeletal and connective tissue disorders 9 1.10 0 0.00 Eye disorders 7 0.86 0 0.00 Injury, poisoning and procedural complications 4 0.49 0 0.00 Psychiatric disorders 3 0.37 0 0.00 Total 816 100.00 41 100.00 Table 3 Distribution of sintilimab related adverse events in different system organs class (SOC) SOC Positive signal number, n Proportion, % Positive PT number, n Proportion, % Blood and lymphatic system disorders 6 14.63 143 17.52 Skin and subcutaneous tissue disorders 6 14.63 99 12.13 Investigations 9 21.95 95 11.64 Hepatobiliary disorders 4 9.76 52 6.37 Endocrine disorders 4 9.76 33 4.04 General disorders and administration site conditions 2 4.88 18 2.21 Infections and infestations 2 4.88 15 1.84 Cardiac disorders 2 4.88 15 1.84 Respiratory, thoracic and mediastinal disorders 1 2.44 11 1.35 Gastrointestinal disorders 2 4.88 7 0.86 Immune system disorders 1 2.44 4 0.49 Renal and urinary disorders 1 2.44 4 0.49 Nervous system disorders 1 2.44 3 0.37 Total 41 100.00 499 61.15 Distribution of AEs in preferred terms (PTs). On the basis of SOCs, the PT of each SOC is determined according to the frequency of occurrence, as shown in Table 4 . According to the frequency of occurrence, the PT corresponds to the 5th ranked SOCs are myelosuppression (PT 10028584, n = 83) in blood and lymphatic system disorders (PT 10005329), rash (PT 10037844, n = 46) in skin and subcutaneous tissue disorders (PT 10040785), white blood cell count decreased (PT 10047942, n = 39) in investigations (PT 10022891), pruritus (PT 10037087, n = 38) in skin and subcutaneous tissue disorders (PT 10040785), and hepatic function abnormal (PT 10019670, n = 33) in hepatobiliary disorders (PT 10019805) respectively. According to the ranking of reporting odds ratio (ROR), the PT corresponding to the first 5 SOC are myocardial necrosis marker increased (ROR = 305.63, PT 10075211) in investigations (PT 10022891), autoimmune hepatitis (ROR = 92.78, PT 10003827) in hepatobiliary disorders (PT 10019805), hypothyroidism (ROR = 70.57, PT 10021114) in endocrine disorders (PT 10014698), myelosuppression (ROR = 55.04, PT 10028584) in blood and lymphatic system disorders (PT 10005329), and liver injury (ROR = 41.40, PT 10067125) in hepatobiliary disorders (PT 10019805) respectively (Table 5 ). Table 4 Frequency of top 30 preferred language (PT) of sintilimab SOC PT Case number, n ROR (95% CI) PRR (Chi-Square) Blood and lymphatic system disorders Myelosuppression 83 55.04(43.86–69.07) 49.54(3954.48) Skin and subcutaneous tissue disorders Rash 46 3.37(2.50–4.54) 3.24(72.29) Investigations White blood cell count decreased 39 23.01(16.68–31.74) 21.95(781.59) Skin and subcutaneous tissue disorders Pruritus 38 3.04(2.20–4.22) 2.95(49.73) Hepatobiliary disorders Hepatic function abnormal 33 30.69(21.66–43.48) 29.49(909.31) Blood and lymphatic system disorders Thrombocytopenia 32 14.09(9.89–20.06) 13.58(373.81) Endocrine disorders Hypothyroidism 23 70.57(46.61-106.83) 68.61(1532.16) Investigations Neutrophil count decreased 18 19.60(12.28–31.27) 19.19(310.62) Infections and infestations Pneumonia 12 4.60(2.60–8.14) 4.55(33.36) Cardiac disorders Myocarditis 12 38.76(21.92–68.54) 38.20(434.77) Respiratory, thoracic and mediastinal disorders Interstitial lung disease 11 20.85(11.50–37.80) 20.58(205.05) General disorders and administration site conditions Chest pain 11 2.36(1.30–4.29) 2.35(8.54) Hepatobiliary disorders Liver injury 11 41.40(22.83–75.06) 40.85(427.67) Blood and lymphatic system disorders Anaemia 10 4.06(2.17–7.57) 4.02(22.74) Investigations Haemoglobin decreased 9 9.43(4.89–18.19) 9.34(67.08) Blood and lymphatic system disorders Pancytopenia 8 12.18(6.07–24.45) 12.07(81.31) General disorders and administration site conditions Hyperpyrexia 7 14.33(6.81–30.16) 14.22(86.05) Blood and lymphatic system disorders Granulocytopenia 7 28.51(13.55-60.00) 28.27(184.17) Investigations Myocardial necrosis marker increased 7 305.63(145.13-643.66) 303.02(2102.79) Investigations Oxygen saturation decreased 6 10.95(4.91–24.45) 10.88(53.86) Investigations Transaminases increased 6 15.95(7.15–35.61) 15.84(83.46) Skin and subcutaneous tissue disorders Dermatitis exfoliative 5 40.63(16.87–97.90) 40.39(192.05) Hepatobiliary disorders Autoimmune hepatitis 5 92.78(38.50-223.59) 92.22(450.91) Investigations Blood pressure decreased 4 5.05(1.89–13.49) 5.03(12.92) Endocrine disorders Adrenal insufficiency 4 34.33(12.85–91.70) 34.16(128.76) Skin and subcutaneous tissue disorders Blister 4 5.92(2.22–15.82) 5.90(16.28) Immune system disorders Anaphylactoid reaction 4 7.14(2.67–19.07) 7.11(21.02) Gastrointestinal disorders Abdominal distension 4 3.47(1.30–9.26) 3.46(6.99) Renal and urinary disorders Renal impairment 4 4.51(1.69–12.05) 4.49(10.87) Investigations Aspartate aminotransferase increased 3 4.04(1.30-12.54) 4.02(6.82) Table 5 Top 30 preferred language (PT) for the positive signal intensity of sintilimab SOC PT Case number, n ROR (95% CI) PRR (Chi-Square) Investigations Myocardial necrosis marker increased 7 305.63(145.13-643.66) 303.02(2102.79) Hepatobiliary disorders Autoimmune hepatitis 5 92.78(38.50-223.59) 92.22(450.91) Endocrine disorders Hypothyroidism 23 70.57(46.61-106.83) 68.61(1532.16) Blood and lymphatic system disorders Myelosuppression 83 55.04(43.86–69.07) 49.54(3954.48) Hepatobiliary disorders Liver injury 11 41.40(22.83–75.06) 40.85(427.67) Skin and subcutaneous tissue disorders Dermatitis exfoliative 5 40.63(16.87–97.90) 40.39(192.05) Cardiac disorders Myocarditis 12 38.76(21.92–68.54) 38.20(434.77) Endocrine disorders Adrenal insufficiency 4 34.33(12.85–91.70) 34.16(128.76) Infections and infestations Encephalitis 3 33.21(10.69–103.20) 33.09(93.35) Hepatobiliary disorders Hepatic function abnormal 33 30.69(21.66–43.48) 29.49(909.31) Blood and lymphatic system disorders Granulocytopenia 7 28.51(13.55-60.00) 28.27(184.17) Investigations White blood cell count decreased 39 23.01(16.68–31.74) 21.95(781.59) Endocrine disorders Thyroid disorder 3 22.60(7.27–70.24) 22.52(61.70) Respiratory, thoracic and mediastinal disorders Interstitial lung disease 11 20.85(11.50–37.80) 20.58(205.05) Investigations Neutrophil count decreased 18 19.60(12.28–31.27) 19.19(310.62) Cardiac disorders Cardiomyopathy 3 19.20(6.18–59.66) 19.13(51.56) Endocrine disorders Hyperthyroidism 3 16.31(5.25–50.69) 16.26(42.96) Investigations Transaminases increased 6 15.95(7.15–35.61) 15.84(83.46) General disorders and administration site conditions Hyperpyrexia 7 14.33(6.81–30.16) 14.22(86.05) Blood and lymphatic system disorders Thrombocytopenia 32 14.09(9.89–20.06) 13.58(373.81) Blood and lymphatic system disorders Pancytopenia 8 12.18(6.07–24.45) 12.07(81.31) Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome 3 11.06(3.56–34.36) 11.02(27.34) Investigations Oxygen saturation decreased 6 10.95(4.91–24.45) 10.88(53.86) Nervous system disorders Epilepsy 3 10.50(3.38–32.62) 10.46(25.69) Investigations Haemoglobin decreased 9 9.43(4.89–18.19) 9.34(67.08) Gastrointestinal disorders Mouth ulceration 3 7.76(2.50–24.10) 7.73(17.59) Immune system disorders Anaphylactoid reaction 4 7.14(2.67–19.07) 7.11(21.02) Skin and subcutaneous tissue disorders Dermatitis 3 6.80(2.19–21.13) 6.78(14.78) Blood and lymphatic system disorders Agranulocytosis 3 6.55(2.11–20.36) 6.53(14.06) Skin and subcutaneous tissue disorders Blister 4 5.92(2.22–15.82) 5.90(16.28) Discussion Over decades, immunotherapy has been an important breakthrough in clinical tumor treatment 5 . Despite representing a pivotal advance in cancer therapy, ICIs such as sintilimab, which selectively targets PD-1/PD-L1 interactions 1 , demand rigorous safety assessment. While clinical trials validate sintilimab’s therapeutic benefits, pharmacovigilance remains critical. Our analysis of real-world global safety data advances understanding of sintilimab’s risk profile to inform clinical management. Our analysis predominantly reflects Asian populations (2020–2024), aligning with evidence suggesting regional variability in AE incidence. It is reported that the incidence of AE differed from Asian to non-Asian 7 . Future expansions to global data are warranted to enhance generalizability. Blood and lymphatic system disorders, skin and subcutaneous tissue disorders, and investigations constituted the three most frequent SOC-level AEs, each exceeding 100 cases and accounting for more than 10% of reports. This ranking remained consistent when evaluating by signal strength (positive PT cases). High AE frequency corresponds with clinical trial observations, and a phase III NSCLC study observed treatment-related AEs in 90% of patients receiving sintilimab 20 . Meanwhile, the treatment-related AEs were dominated with lymphopenia, neutropenia and leukopenia, when the patients with HER2-negative locally advanced gastric cancer or cancer at the gastroesophageal junction were treated with combination of sintilimaband fluorouracil, leucovorin, oxaliplatin, or docetaxel 21 . Treating recurrent or metastatic cervical cancer with the combination of sintilimab andanrotinib, the predominant AEs were hypothyroidism, elevated aspartate aminotransferase levels, and hypertension 22 . These discrepancies in reported AE profiles across studies likely stem from sample size variations and differential concomitant medication use. Critically, our pharmacovigilance data suggest sintilimab’s organ-specific toxicity profile may be intrinsic to its mechanism that targeting immune checkpoints expressed across tissues rather than tumor-type dependent. Further mechanistic studies are essential to elucidate these etiologies and optimize risk mitigation strategies. Our Preferred Term (PT) analysis identified myelosuppression, rash, and decreased white blood cell count as the most frequent adverse events, which are all immunologically mediated. This aligns with a recent a multicentre, open-label, parallel-group, randomised, controlled phase 3 trial data where most immune-related AEs were grade 1–2 and rash predominated among grade 3–4 immune-related AEs 23 . In this study, two fatal immune-related events (death, grade 5 AEs) were reported. Notably, hematologic toxicities like anemia and decreased white blood cel consistently emerge in sintilimab combination therapies, though their precise mechanistic relationship to PD-1 inhibition (versus chemotherapeutic effects) requires further investigation 24 – 26 . It has been agreed that AEs such as myelosuppression and cytopenia are the side effects brought by chemotherapy 27 , 28 . Unexpectedly, increased myocardial necrosis markers ranked highest by ROR methodology, suggesting potential cardiotoxicity. Xu et al. conducted a phase III clinical trial in 650 patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma in 62 hospitals in China from 2019 to 2020 to compare the efficacy of sintilimab combined chemotherapy with placebo combined chemotherapy 29 . In this study, the incidence of cardiac treatment-related AEs in all grades in the sintilimab group was 10.7%, which was slightly higher than that in the placebo group (10.3%) 30 . Myocarditis occurred in one patient (0.3%), while heart failure promted sintilimab discontinuation in two others. Although the incidence of cardiac treatment-related AEs may be not high, the damage of important organs deserves vigilance. Future pharmacovigilance efforts should prioritize AE grading stratification alongside SOC/PT categorization to better inform risk-benefit assessments. This study establishes foundational real-world evidence for sintilimab's hematologic, dermatologic, and cardiac safety profiles to guide clinical decision-making. Conclusion To our knowledge, this study establishes the first systematic profile of sintilimab-associated AEs at SOC and PT levels using WHO-VigiAccess data. While providing critical real-world evidence to guide clinical risk assessment, these findings require further mechanistic research to elucidate sintilimab’s safety pathophysiology. Methods Data collection. The pharmacovigilance data of sintilimab comes from the reports of WHO-VigiAccess database ( https://www.vigiaccess.org ) from 2020 to 2024. After identifying and deleting duplicate reports, 487 reports were finally included in the study. According to the SOC and PT of Medical Dictionary for Regulatory Activities (MedDRA), the data extracted from AE include patient demographic data, such as gender, age, reporting schedule, and geographical distribution. The final correlation AEs of sintilimab is identified according to SOC and PT levels. Statistical analysis. Disproportionality analysis was used to determine the potential correlation between sintilimab and AEs. These statistical methods include calculating reporting odds ratio (ROR) and the proportional reporting ratio (PRR). Specific calculation methods can refer to Table 6 and Table 7 . A retrospective quantitative approach was utilized in this study. Table 6 Two-by-two contingency table for disproportionality analysis. Item Target adverse events reported Other adverse events reported Total Target drugs a b a + b Other drugs c d c + d Total a + c b + d a + b + c + d Table 7 The principles of disproportionate measurement and the criteria for signal detection. Method Calculation formula ໿Criteria ROR \(\:\text{R}\text{O}\text{R}=\frac{\text{a}\:/\:\text{c}}{b\:/\:d}\) a ≥ 3 ROR ≥ 1 95%CI (lower limit) > 1 \(\:SE\left(lnROR\right)=\sqrt{\frac{1}{\text{a}}+\frac{1}{\text{b}}+\frac{1}{\text{c}}+\frac{1}{\text{d}}}\) \(\:95\%CI=\:{\text{e}}^{\text{ln}\left(ROR\right)\pm\:1.96se}\) PRR \(\:\text{P}\text{R}\text{R}=\frac{\text{a}\:/\:(\text{a}+\text{b})}{c\:/\:(c+d)}\) a ≥ 3 PRR ≥ 2 95%CI (lower limit) > 1 \(\:SE\left(lnPRR\right)=\sqrt{\frac{1}{\text{a}}-\frac{1}{\text{a}+\text{b}}+\frac{1}{\text{c}}-\frac{1}{\text{c}+\text{d}}}\) \(\:95\%CI=\:{\text{e}}^{\text{ln}\left(PRR\right)\pm\:1.96se}\) \(\:{\chi\:}2\:=\frac{\:{(\text{a}\text{d}-\text{b}\text{c})}^{2}(\text{a}+\text{b}+\text{c}+\text{d})}{(\:\text{a}+\text{b})(\text{a}+\text{c})(\text{c}+\text{d})(\text{b}+\text{d})}\) a ≥ 3 PRR ≥ 2 \(\:{\chi\:}2\ge\:4\) \(\:SE\left(lnEBGM\right)=\sqrt{\frac{1}{\text{a}}+\frac{1}{\text{b}}+\frac{1}{\text{c}}+\frac{1}{\text{d}}}\) \(\:95\%CI=\:{\text{e}}^{\text{ln}\left(EBGM\right)\pm\:1.96se}\) Declarations Competing interests The authors declare no competing interests. Ethics approval and consent to participate Not applicable. The data used in this study came from the WHO VigiAccess Database so this study was deemed non-human subject related research. AI statement In this study, DeepSeek was used to check for grammatical errors in the text, polish the language, but no DeepSeek was used for writing. Funding This work was supported by the 2022–2023 Guangxi Zhuang Autonomous Region Health Commission Comprehensive Clinical Evaluation of Drugs Subject Funding Project (Project contract number: YPPJ005); Guangxi drug safety research project (Project number: [2024]010); and Hospital Pharmaceutical Research Project of Guangxi Pharmaceutical Society (Contract Number.: GXYXH-202403) Author Contribution Youjia Guo, and Li Wen: Validation, Visualization, and Writing–original draft; Fangcheng Jiang, Liling Pan, and Lei He: Data curation, Formal Analysis, and Methodology; Zhaoji Liu, and Qiong Wu: Data curation, and Formal Analysis; Zefeng Lai: Supervision, Validation, and Writing-review and editing; Qichun Huang, and Yan Li: Conceptualization, Funding acquisition, Project administration, Supervision, Validation, and Writing-review and editing. Data Availability The original data for this article were obtained from the VigiAccess website and can be shared with investigators. References Zhou C, Wu L, Fan Y, et al. Sintilimab Plus Platinum and Gemcitabine as First-Line Treatment for Advanced or Metastatic Squamous NSCLC: Results From a Randomized, Double-Blind, Phase 3 Trial (ORIENT-12). J Thorac Oncol Sep. 2021;16(9):1501–11. 10.1016/j.jtho.2021.04.011 . Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin Jan-Feb. 2025;75(1):10–45. 10.3322/caac.21871 . Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin May-Jun. 2024;74(3):229–63. 10.3322/caac.21834 . Zhang C, Sun YX, Yi DC, et al. Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant NSCLC: Phase 2 trial interim results (NEOTIDE/CTONG2104). Cell Rep Med Jul. 2024;16(7):101615. 10.1016/j.xcrm.2024.101615 . Li Y, Liang X, Li H, Chen X. Efficacy and safety of immune checkpoint inhibitors for advanced non-small cell lung cancer with or without PD-L1 selection: A systematic review and network meta-analysis. Chin Med J (Engl) Sep. 2023;20(18):2156–65. 10.1097/cm9.0000000000002750 . Shi Y, Wu L, Yu X, et al. Sintilimab versus docetaxel as second-line treatment in advanced or metastatic squamous non-small-cell lung cancer: an open-label, randomized controlled phase 3 trial (ORIENT-3). Cancer Commun (Lond) Dec. 2022;42(12):1314–30. 10.1002/cac2.12385 . Yang Y, Wang Z, Fang J, et al. Efficacy and Safety of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC: a Randomized, Double-Blind, Phase 3 Study (Oncology pRogram by InnovENT anti-PD-1-11). J Thorac Oncol Oct. 2020;15(10):1636–46. 10.1016/j.jtho.2020.07.014 . Yang Y, Sun J, Wang Z, et al. Updated Overall Survival Data and Predictive Biomarkers of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC in the Phase 3 ORIENT-11 Study. J Thorac Oncol Dec. 2021;16(12):2109–20. 10.1016/j.jtho.2021.07.015 . Lu S, Wu L, Jian H, et al. Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): first interim results from a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol Sep. 2022;23(9):1167–79. 10.1016/s1470-2045(22)00382-5 . Gao Z, Teng J, Qiao R, et al. Efficacy and Safety of a Therapy Combining Sintilimab and Chemotherapy With Cryoablation in the First-Line Treatment of Advanced Nonsquamous Non-Small Cell Lung Cancer: Protocol for a Phase II, Pilot, Single-Arm, Single-Center Study. JMIR Res Protoc Nov. 2024;8:13:e64950. 10.2196/64950 . Ni J, Wang X, Wu L, et al. Sintilimab in combination with stereotactic body radiotherapy and granulocyte-macrophage colony-stimulating factor in metastatic non-small cell lung cancer: The multicenter SWORD phase 2 trial. Nat Commun Aug. 2024;22(1):7242. 10.1038/s41467-024-51807-7 . Zhou X, Zhou L, Yao Z, et al. Safety and Tolerability of Low-Dose Radiation and Stereotactic Body Radiotherapy + Sintilimab for Treatment-Naïve Stage IV PD-L1 + Non-Small Cell Lung Cancer Patients. Clin Cancer Res Oct. 2023;13(20):4098–108. 10.1158/1078-0432.Ccr-23-0315 . Cappuyns S, Corbett V, Yarchoan M, Finn RS, Llovet JM. Critical Appraisal of Guideline Recommendations on Systemic Therapies for Advanced Hepatocellular Carcinoma: A Review. JAMA Oncol. Mar 2024;1(3):395–404. 10.1001/jamaoncol.2023.2677 . Fulgenzi CAM, D'Alessio A, Airoldi C, et al. Comparative efficacy of novel combination strategies for unresectable hepatocellular carcinoma: A network metanalysis of phase III trials. Eur J Cancer Oct. 2022;174:57–67. 10.1016/j.ejca.2022.06.058 . Liu L, Bai H, Wang C, et al. Efficacy and Safety of First-Line Immunotherapy Combinations for Advanced NSCLC: A Systematic Review and Network Meta-Analysis. J Thorac Oncol Jul. 2021;16(7):1099–117. 10.1016/j.jtho.2021.03.016 . Gao S, Li N, Gao S, et al. Neoadjuvant PD-1 inhibitor (Sintilimab) in NSCLC. J Thorac Oncol May. 2020;15(5):816–26. 10.1016/j.jtho.2020.01.017 . Maggie Liu SY, Huang J, Deng JY, et al. PD-L1 expression guidance on sintilimab versus pembrolizumab with or without platinum-doublet chemotherapy in untreated patients with advanced non-small cell lung cancer (CTONG1901): A phase 2, randomized, controlled trial. Sci Bull (Beijing) Feb. 2024;26(4):535–43. 10.1016/j.scib.2023.12.046 . Liang Q, Liao X, Huang Y et al. Safety study on adverse events of zanubrutinib based on WHO-VigiAccess and FAERS databases. Expert Opin Drug Saf Oct 15 2024:1–8. 10.1080/14740338.2024.2416917 Zhou Q, Xie Q, Liu Q, et al. DNA methylation inhibitors adverse reaction characteristic analysis: a descriptive analysis from WHO-VigiAccess. Front Pharmacol. 2024;15:1470148. 10.3389/fphar.2024.1470148 . Zhang P, Dai J, Sun F, et al. Neoadjuvant Sintilimab and Chemotherapy for Resectable Stage IIIA Non-Small Cell Lung Cancer. Ann Thorac Surg Sep. 2022;114(3):949–58. 10.1016/j.athoracsur.2022.01.039 . Li N, Li Z, Fu Q, et al. Efficacy and safety of neoadjuvant sintilimab in combination with FLOT chemotherapy in patients with HER2-negative locally advanced gastric or gastroesophageal junction adenocarcinoma: an investigator-initiated, single-arm, open-label, phase II study. Int J Surg Apr. 2024;1(4):2071–84. 10.1097/js9.0000000000001119 . Xu Q, Wang J, Sun Y, et al. Efficacy and Safety of Sintilimab Plus Anlotinib for PD-L1-Positive Recurrent or Metastatic Cervical Cancer: A Multicenter, Single-Arm, Prospective Phase II Trial. J Clin Oncol Jun. 2022;1(16):1795–805. 10.1200/jco.21.02091 . Liu X, Zhang Y, Yang KY, et al. Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial. Lancet Jun. 2024;22(10445):2720–31. 10.1016/s0140-6736(24)00594-4 . Jiang H, Yu X, Li N, et al. Efficacy and safety of neoadjuvant sintilimab, oxaliplatin and capecitabine in patients with locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma: early results of a phase 2 study. J Immunother Cancer Mar. 2022;10(3). 10.1136/jitc-2021-003635 . Wang Y, Zhao J, Liang H, et al. Efficacy and safety of sintilimab plus albumin-bound-paclitaxel in recurrent or metastatic cervical cancer: a multicenter, open-label, single-arm, phase II trial. EClinicalMedicine Nov. 2023;65:102274. 10.1016/j.eclinm.2023.102274 . Que Y, Wang J, Sun F, et al. Safety and clinical efficacy of sintilimab (anti-PD-1) in pediatric patients with advanced or recurrent malignancies in a phase I study. Signal Transduct Target Ther Oct. 2023;13(1):392. 10.1038/s41392-023-01636-9 . Zhang QL, Wu TT, Han Y, Zheng ZM, Zhang Y. Chemotherapy-Induced Myelosuppression in Esophageal Cancer Patients: Risks and Suggestions for Its Management. Curr Med Sci Jun. 2022;42(3):530–7. 10.1007/s11596-022-2587-3 . Boccia R, Glaspy J, Crawford J, Aapro M. Chemotherapy-Induced Neutropenia and Febrile Neutropenia in the US: A Beast of Burden That Needs to Be Tamed? Oncologist . Aug. 2022;5(8):625–36. 10.1093/oncolo/oyac074 . Xu J, Jiang H, Pan Y, et al. Sintilimab Plus Chemotherapy for Unresectable Gastric or Gastroesophageal Junction Cancer: The ORIENT-16 Randomized Clinical Trial. Jama Dec. 2023;5(21):2064–74. 10.1001/jama.2023.19918 . Xu J, Sintilimab, Toxicity-Reply C. Jama . Apr 16 2024;331(15):1334–1335. 10.1001/jama.2024.0676 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 14 Nov, 2025 Reviewers invited by journal 14 Nov, 2025 Editor invited by journal 22 Oct, 2025 Editor assigned by journal 21 Oct, 2025 Submission checks completed at journal 21 Oct, 2025 First submitted to journal 20 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7907424","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":550213047,"identity":"12b9189f-89ab-480c-9325-5dbad79ea90b","order_by":0,"name":"Youjia Guo","email":"","orcid":"","institution":"Guangxi Medical University Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Youjia","middleName":"","lastName":"Guo","suffix":""},{"id":550213048,"identity":"4274f099-a0c9-4800-88e7-a6a27c7f77a4","order_by":1,"name":"Li Wen","email":"","orcid":"","institution":"Guangxi Center for Food and Drug Evaluation and Inspection","correspondingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Wen","suffix":""},{"id":550213049,"identity":"404084a9-93f1-4685-bca2-50c6b10e8cfc","order_by":2,"name":"Fangcheng Jiang","email":"","orcid":"","institution":"Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Fangcheng","middleName":"","lastName":"Jiang","suffix":""},{"id":550213050,"identity":"eb8f76cc-1d41-45ce-be53-4c285cdff2a9","order_by":3,"name":"Liling Pan","email":"","orcid":"","institution":"Guangxi Medical University Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Liling","middleName":"","lastName":"Pan","suffix":""},{"id":550213051,"identity":"1f14b5e3-f3af-40fd-a22e-d115b64b6d81","order_by":4,"name":"Lei He","email":"","orcid":"","institution":"Guangxi Medical University Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Lei","middleName":"","lastName":"He","suffix":""},{"id":550213052,"identity":"20d37dd3-574f-45ba-ae6d-0748358bf469","order_by":5,"name":"Zhaoji Liu","email":"","orcid":"","institution":"Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhaoji","middleName":"","lastName":"Liu","suffix":""},{"id":550213054,"identity":"44bc01e9-05e4-4fa7-b608-4d5cf84ed954","order_by":6,"name":"Qiong Wu","email":"","orcid":"","institution":"Guangxi Medical University Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Qiong","middleName":"","lastName":"Wu","suffix":""},{"id":550213055,"identity":"8e02b2d3-85c5-4fc3-95f1-ebb9b5c47256","order_by":7,"name":"Zefeng Lai","email":"","orcid":"","institution":"Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zefeng","middleName":"","lastName":"Lai","suffix":""},{"id":550213056,"identity":"e91cc421-ddbe-49b5-bf8f-9b6b604f4334","order_by":8,"name":"Qichun Huang","email":"","orcid":"","institution":"Guangxi Medical University Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Qichun","middleName":"","lastName":"Huang","suffix":""},{"id":550213057,"identity":"4e38b59d-044c-4318-936f-0e7b27cd6085","order_by":9,"name":"Yan Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIiWNgGAWjYBACNv7mgw8/GPyvtz/MfIA4LXwSx5KNJQqYExiOsyUQp0WOIcdMgucDUMt5HgMiHcZwxkxCwoAtj7GZ5+ONNwx2croNhLQwtxVbFBjwFDMz8262nMOQbGx2gKAthzfekDCQYGxj5t0mzcNwIHEbYS0JBhI8BgaMPcw8z4jVkmIE1JKQOIOZh41ILeBANjhgbMDMZmw5x4AIv8j3g6LyzwE5A/7DD2+8qbCTI6gFBUgQGzXIWkjVMQpGwSgYBSMCAAA0ojuPpbxt4gAAAABJRU5ErkJggg==","orcid":"","institution":"Guangxi Medical University Cancer Hospital","correspondingAuthor":true,"prefix":"","firstName":"Yan","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2025-10-20 16:10:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7907424/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7907424/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":96745433,"identity":"364c4482-4d16-4e8a-8e3e-fa87f20daba8","added_by":"auto","created_at":"2025-11-25 15:50:45","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":274575,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscriptwithauthordetails.docx","url":"https://assets-eu.researchsquare.com/files/rs-7907424/v1/dd021493c2c95e99de09efe0.docx"},{"id":96745432,"identity":"81cac816-264d-4773-9184-90557309c7c3","added_by":"auto","created_at":"2025-11-25 15:50:45","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":9778,"visible":true,"origin":"","legend":"","description":"","filename":"ba08434e0f7d44a88d46f32c350e25ff.json","url":"https://assets-eu.researchsquare.com/files/rs-7907424/v1/8db5287763bb978c4715d4ec.json"},{"id":96745434,"identity":"1823fd75-a7be-4a8f-a010-2b017b344f4a","added_by":"auto","created_at":"2025-11-25 15:50:45","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":129968,"visible":true,"origin":"","legend":"","description":"","filename":"ba08434e0f7d44a88d46f32c350e25ff1enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7907424/v1/b15efc24be4a683856b20070.xml"},{"id":96745431,"identity":"85de6fb2-5d0c-42f3-b5dd-bf37018ac2e6","added_by":"auto","created_at":"2025-11-25 15:50:45","extension":"png","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":32623,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7907424/v1/721795807ebc1393d49394a5.png"},{"id":96913489,"identity":"20e7d428-b46c-49ca-9d9a-bf09d6efe7df","added_by":"auto","created_at":"2025-11-27 14:02:16","extension":"xml","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":129709,"visible":true,"origin":"","legend":"","description":"","filename":"ba08434e0f7d44a88d46f32c350e25ff1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7907424/v1/30ed4fb47f577c98eb7a34a4.xml"},{"id":96745436,"identity":"3959262d-307a-478f-a1c3-353a875f6895","added_by":"auto","created_at":"2025-11-25 15:50:45","extension":"html","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":136911,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7907424/v1/d07dd7bed49eae6042b955ca.html"},{"id":96914651,"identity":"6199dce6-07e7-49d1-b35f-b8c901755ff2","added_by":"auto","created_at":"2025-11-27 14:06:12","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":141749,"visible":true,"origin":"","legend":"\u003cp\u003eThe main statistical analysis results. A. The cumulative number of adverse events (AEs) in system organ class (SOC); B. The positive signal number of AEs in SOC; C. Frequency of top 5 preferred term (PT) of sintilimab; D. Top 5 PT for the positive signal intensity of sintilimab.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7907424/v1/7416757db214a19fa2d29558.jpeg"},{"id":96922349,"identity":"d2d8637a-33b1-4308-8254-5cacebcf5c41","added_by":"auto","created_at":"2025-11-27 14:19:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1202466,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7907424/v1/c4fac213-8c82-4c91-9c50-5de870705473.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Sintilimab Pharmacovigilance in Real-World Practice: Analysis Utilizing the WHO VigiAccess Database","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSintilimab, a human immunoglobulin G4 (IgG4) monoclonal antibody, selectively binds programmed cell death protein 1 (PD-1) on T-cell surfaces to block the PD-1/programmed death-ligand 1 (PD-L1) pathway, thereby restoring lymphocyte-mediated antitumor activity for therapeutic efficacy in tumors \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Recently, sintilimab has been approved for the therapy of several solid malignancies, including non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), and classical Hodgkin's lymphoma. Among these, NSCLC and HCC remain the leading cause of global cancer mortality, posing a significant public health challenge \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eNSCLC represents the predominant histological subtype of lung cancer. In Asian populations, approximately half of NSCLC patients carry epidermal growth factor receptor (EGFR) mutations, for which EGFR tyrosine kinase inhibitors (TKIs) serve as the standard first-line therapy \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. For those without detectable driver mutations, immune checkpoint inhibitors (ICIs), including sintilimab, have emerged as foundational treatments for advanced NSCLC \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Previous study has demonstrated that sintilimab significantly improved the prognosis of patients with previously treated locally advanced or metastatic squamous-cell NSCLC \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Furthermore, a randomized, double-blind, phase III clinical trial showed that sintilimab combined with chemotherapy or other modalities prolonged the progression-free survival and overall survival of patients with NSCLC without EGFR or ALK mutation compared with chemotherapy alone \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Evidence also supports combining PD-1 inhibitors with VEGF-targeted agents or local therapies such as radiotherapy and cryoablation to overcome TKI resistance \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eHCC is the most common form of liver cancer. In the first-line therapies of advanced HCC, the combination of sintilimab and IBI305 (a bevacizumab biosimilar) achieved a European Society for Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS) score of 5, indicating a significant clinical benefit \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. This regimen demonstrated significant improvement in overall survival and progression-free survival benefits compared to sorafenib in Chinese patients with unresectable hepatitis B virus-related HCC in China, alongside an acceptable safety profile \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIn summary, sintilimab demonstrates a wide range of clinical applicability, with numerous studies affirming its significant therapeutic efficacy. However, meta-analyses studies indicate that treatment intensification, whether through immunotherapy or anti-angiogenic agents, or combination regimens, elevates toxicity risks and is associated with higher adverse event (AE) rates \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Even single treatment with PD-1 inhibitors results in AEs. Notabley, sintilimab is associated with a higher incidence of rash compared to pembrolizumab \u003csup\u003e16 17\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eTo date, Sintilima\u0026rsquo;s distinct AE profile remains incompletely characterized in real-world settings and further prospective pharmacovigilance studies are needed to delineate its distinct safety spectrum. WHO-VigiAccess synthesized the reports of AEs from various countries and regions, as a real-world data warehouse of AEs, providing a global perspective of drug safety information \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. This pharmacovigilance study addresses this gap by analyzing sintilimab-associated AEs reported in the WHO VigiAccess database from 2020\u0026ndash;2024, predominantly across Asian populations, to inform safer clinical application.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cb\u003eBasic characteristic of AEs-related patients.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes cohort demographics.​​ Males predominated (64.07%), while females comprised 35.73% of cases. In terms of age distribution, patients aged\u0026thinsp;\u0026ge;\u0026thinsp;45 years constituted the majority (92.7% total), most notably those aged 45\u0026ndash;64 years (46.61%). The cohort of 486 patients was predominantly Asian (99.79%), with reports concentrated in 2020 (30.80%) and 2021 (68.99%).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eThe basic demographic data related to adverse events.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCase number (Proportion, %)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e174(35.73)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e312(64.07)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnknown\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1(0.21)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u0026ndash;11 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1(0.21)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e18\u0026ndash;44 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e44(9.03)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e45\u0026ndash;64 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e227(46.61)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e65\u0026ndash;74 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e151(31.01)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e75 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e60(12.32)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnknown\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4(0.82)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRegion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAmerica\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1(0.21)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAsia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e486(99.79)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReporting year\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2020\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e150(30.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2021\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e336(68.99)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2024\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1(0.21)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eDistribution of AEs in system organs class (SOC).\u003c/b\u003e\u003c/p\u003e\u003cp\u003ePrimary AE distributions appear in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Specifically, the distribution of positive signals of sintilimab-related AEs at the level of systemic organ classification are described in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. According to the cumulative number of AEs cases in SOC, the top 5 SOCs are blood and lymphatic system disorders (SOC code: 10005329, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;152), skin and subcutaneous tissuedisorders (SOC code: 10040785, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;135), investigations (SOC code: 10022891, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;112), general disorders and administration site conditions (SOC code: 10018065, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;79), and gastrointestinal disorders (SOC code: 10017947, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;65). According to the positive PT number of AEs in SOC (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), the top 5 SOC are blood and lymphatic system disorders (SOC code: 10005329, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;143), skin and subcutaneous tissue disorders (SOC code: 10040785, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;99), investigations (SOC code: 10022891, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;95), hepatobiliary disorders (SOC code: 10019805, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;52), and endocrine disorders (SOC code: 10014698, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;33).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDistribution of sintilimab related adverse events in different system organs class (SOC)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSOC\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCase number, \u003cem\u003en\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eproportion, %\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePositive signal number, \u003cem\u003en\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eproportion, %\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood and lymphatic system disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e152\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e18.63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e14.63\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSkin and subcutaneous tissue disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e135\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16.54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e14.63\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvestigations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e112\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e13.73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e21.95\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGeneral disorders and administration site conditions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4.88\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGastrointestinal disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7.97\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4.88\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHepatobiliary disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e9.76\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndocrine disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e9.76\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardiac disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4.88\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRespiratory, thoracic and mediastinal disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.44\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInfections and infestations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4.88\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNervous system disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.44\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRenal and urinary disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.72\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.44\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMetabolism and nutrition disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eImmune system disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.44\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVascular disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMusculoskeletal and connective tissue disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEye disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInjury, poisoning and procedural complications\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePsychiatric disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e816\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e100.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e100.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDistribution of sintilimab related adverse events in different system organs class (SOC)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSOC\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePositive signal number, \u003cem\u003en\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eProportion, %\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePositive PT number, \u003cem\u003en\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eProportion, %\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood and lymphatic system disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14.63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e143\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e17.52\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSkin and subcutaneous tissue disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14.63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e12.13\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvestigations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e21.95\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e95\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e11.64\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHepatobiliary disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e6.37\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndocrine disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4.04\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGeneral disorders and administration site conditions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.88\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.21\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInfections and infestations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.88\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.84\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardiac disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.88\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.84\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRespiratory, thoracic and mediastinal disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.35\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGastrointestinal disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.88\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.86\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eImmune system disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.49\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRenal and urinary disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.49\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNervous system disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.37\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e 41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e100.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e499\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e61.15\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eDistribution of AEs in preferred terms (PTs).\u003c/b\u003e\u003c/p\u003e\u003cp\u003eOn the basis of SOCs, the PT of each SOC is determined according to the frequency of occurrence, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. According to the frequency of occurrence, the PT corresponds to the 5th ranked SOCs are myelosuppression (PT 10028584, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;83) in blood and lymphatic system disorders (PT 10005329), rash (PT 10037844, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;46) in skin and subcutaneous tissue disorders (PT 10040785), white blood cell count decreased (PT 10047942, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;39) in investigations (PT 10022891), pruritus (PT 10037087, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;38) in skin and subcutaneous tissue disorders (PT 10040785), and hepatic function abnormal (PT 10019670, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;33) in hepatobiliary disorders (PT 10019805) respectively. According to the ranking of reporting odds ratio (ROR), the PT corresponding to the first 5 SOC are myocardial necrosis marker increased (ROR\u0026thinsp;=\u0026thinsp;305.63, PT 10075211) in investigations (PT 10022891), autoimmune hepatitis (ROR\u0026thinsp;=\u0026thinsp;92.78, PT 10003827) in hepatobiliary disorders (PT 10019805), hypothyroidism (ROR\u0026thinsp;=\u0026thinsp;70.57, PT 10021114) in endocrine disorders (PT 10014698), myelosuppression (ROR\u0026thinsp;=\u0026thinsp;55.04, PT 10028584) in blood and lymphatic system disorders (PT 10005329), and liver injury (ROR\u0026thinsp;=\u0026thinsp;41.40, PT 10067125) in hepatobiliary disorders (PT 10019805) respectively (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eFrequency of top 30 preferred language (PT) of sintilimab\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSOC\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePT\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCase number, \u003cem\u003en\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eROR (95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePRR (Chi-Square)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood and lymphatic system disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMyelosuppression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e83\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e55.04(43.86\u0026ndash;69.07)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e49.54(3954.48)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSkin and subcutaneous tissue disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRash\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.37(2.50\u0026ndash;4.54)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3.24(72.29)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvestigations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eWhite blood cell count decreased\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e23.01(16.68\u0026ndash;31.74)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e21.95(781.59)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSkin and subcutaneous tissue disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePruritus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.04(2.20\u0026ndash;4.22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.95(49.73)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHepatobiliary disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHepatic function abnormal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e30.69(21.66\u0026ndash;43.48)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e29.49(909.31)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood and lymphatic system disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eThrombocytopenia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e14.09(9.89\u0026ndash;20.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e13.58(373.81)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndocrine disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHypothyroidism\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e70.57(46.61-106.83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e68.61(1532.16)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvestigations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNeutrophil count decreased\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e19.60(12.28\u0026ndash;31.27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e19.19(310.62)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInfections and infestations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePneumonia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.60(2.60\u0026ndash;8.14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4.55(33.36)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardiac disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMyocarditis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e38.76(21.92\u0026ndash;68.54)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e38.20(434.77)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRespiratory, thoracic and mediastinal disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eInterstitial lung disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e20.85(11.50\u0026ndash;37.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e20.58(205.05)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGeneral disorders and administration site conditions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eChest pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.36(1.30\u0026ndash;4.29)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.35(8.54)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHepatobiliary disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLiver injury\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e41.40(22.83\u0026ndash;75.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e40.85(427.67)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood and lymphatic system disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAnaemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.06(2.17\u0026ndash;7.57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4.02(22.74)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvestigations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHaemoglobin decreased\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9.43(4.89\u0026ndash;18.19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e9.34(67.08)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood and lymphatic system disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePancytopenia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e12.18(6.07\u0026ndash;24.45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e12.07(81.31)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGeneral disorders and administration site conditions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHyperpyrexia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e14.33(6.81\u0026ndash;30.16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e14.22(86.05)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood and lymphatic system disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGranulocytopenia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e28.51(13.55-60.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e28.27(184.17)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvestigations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMyocardial necrosis marker increased\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e305.63(145.13-643.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e303.02(2102.79)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvestigations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOxygen saturation decreased\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e10.95(4.91\u0026ndash;24.45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e10.88(53.86)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvestigations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTransaminases increased\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e15.95(7.15\u0026ndash;35.61)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e15.84(83.46)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSkin and subcutaneous tissue disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDermatitis exfoliative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e40.63(16.87\u0026ndash;97.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e40.39(192.05)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHepatobiliary disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAutoimmune hepatitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e92.78(38.50-223.59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e92.22(450.91)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvestigations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBlood pressure decreased\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5.05(1.89\u0026ndash;13.49)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e5.03(12.92)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndocrine disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAdrenal insufficiency\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e34.33(12.85\u0026ndash;91.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e34.16(128.76)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSkin and subcutaneous tissue disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBlister\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5.92(2.22\u0026ndash;15.82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e5.90(16.28)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eImmune system disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAnaphylactoid reaction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e7.14(2.67\u0026ndash;19.07)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e7.11(21.02)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGastrointestinal disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAbdominal distension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.47(1.30\u0026ndash;9.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3.46(6.99)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRenal and urinary disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRenal impairment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.51(1.69\u0026ndash;12.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4.49(10.87)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvestigations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAspartate aminotransferase increased\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.04(1.30-12.54)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4.02(6.82)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eTop 30 preferred language (PT) for the positive signal intensity of sintilimab\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSOC\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePT\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCase number, n\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eROR (95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePRR (Chi-Square)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvestigations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMyocardial necrosis marker increased\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e305.63(145.13-643.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e303.02(2102.79)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHepatobiliary disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAutoimmune hepatitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e92.78(38.50-223.59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e92.22(450.91)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndocrine disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHypothyroidism\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e70.57(46.61-106.83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e68.61(1532.16)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood and lymphatic system disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMyelosuppression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e83\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e55.04(43.86\u0026ndash;69.07)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e49.54(3954.48)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHepatobiliary disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLiver injury\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e41.40(22.83\u0026ndash;75.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e40.85(427.67)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSkin and subcutaneous tissue disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDermatitis exfoliative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e40.63(16.87\u0026ndash;97.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e40.39(192.05)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardiac disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMyocarditis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e38.76(21.92\u0026ndash;68.54)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e38.20(434.77)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndocrine disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAdrenal insufficiency\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e34.33(12.85\u0026ndash;91.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e34.16(128.76)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInfections and infestations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEncephalitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e33.21(10.69\u0026ndash;103.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e33.09(93.35)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHepatobiliary disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHepatic function abnormal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e30.69(21.66\u0026ndash;43.48)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e29.49(909.31)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood and lymphatic system disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGranulocytopenia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e28.51(13.55-60.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e28.27(184.17)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvestigations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eWhite blood cell count decreased\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23.01(16.68\u0026ndash;31.74)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e21.95(781.59)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndocrine disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eThyroid disorder\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e22.60(7.27\u0026ndash;70.24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e22.52(61.70)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRespiratory, thoracic and mediastinal disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eInterstitial lung disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20.85(11.50\u0026ndash;37.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e20.58(205.05)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvestigations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNeutrophil count decreased\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19.60(12.28\u0026ndash;31.27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e19.19(310.62)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardiac disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCardiomyopathy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19.20(6.18\u0026ndash;59.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e19.13(51.56)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndocrine disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHyperthyroidism\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16.31(5.25\u0026ndash;50.69)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e16.26(42.96)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvestigations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTransaminases increased\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15.95(7.15\u0026ndash;35.61)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e15.84(83.46)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGeneral disorders and administration site conditions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHyperpyrexia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14.33(6.81\u0026ndash;30.16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e14.22(86.05)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood and lymphatic system disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eThrombocytopenia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14.09(9.89\u0026ndash;20.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e13.58(373.81)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood and lymphatic system disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePancytopenia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12.18(6.07\u0026ndash;24.45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e12.07(81.31)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSkin and subcutaneous tissue disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePalmar-plantar erythrodysaesthesia syndrome\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11.06(3.56\u0026ndash;34.36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e11.02(27.34)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvestigations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOxygen saturation decreased\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10.95(4.91\u0026ndash;24.45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e10.88(53.86)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNervous system disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEpilepsy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10.50(3.38\u0026ndash;32.62)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e10.46(25.69)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvestigations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHaemoglobin decreased\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9.43(4.89\u0026ndash;18.19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e9.34(67.08)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGastrointestinal disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMouth ulceration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.76(2.50\u0026ndash;24.10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e7.73(17.59)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eImmune system disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAnaphylactoid reaction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.14(2.67\u0026ndash;19.07)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e7.11(21.02)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSkin and subcutaneous tissue disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDermatitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.80(2.19\u0026ndash;21.13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e6.78(14.78)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood and lymphatic system disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAgranulocytosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.55(2.11\u0026ndash;20.36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e6.53(14.06)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSkin and subcutaneous tissue disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBlister\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.92(2.22\u0026ndash;15.82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e5.90(16.28)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOver decades, immunotherapy has been an important breakthrough in clinical tumor treatment \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Despite representing a pivotal advance in cancer therapy, ICIs such as sintilimab, which selectively targets PD-1/PD-L1 interactions \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e, demand rigorous safety assessment. While clinical trials validate sintilimab\u0026rsquo;s therapeutic benefits, pharmacovigilance remains critical. Our analysis of real-world global safety data advances understanding of sintilimab\u0026rsquo;s risk profile to inform clinical management.\u003c/p\u003e\u003cp\u003eOur analysis predominantly reflects Asian populations (2020\u0026ndash;2024), aligning with evidence suggesting regional variability in AE incidence. It is reported that the incidence of AE differed from Asian to non-Asian \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Future expansions to global data are warranted to enhance generalizability. Blood and lymphatic system disorders, skin and subcutaneous tissue disorders, and investigations constituted the three most frequent SOC-level AEs, each exceeding 100 cases and accounting for more than 10% of reports. This ranking remained consistent when evaluating by signal strength (positive PT cases). High AE frequency corresponds with clinical trial observations, and a phase III NSCLC study observed treatment-related AEs in 90% of patients receiving sintilimab \u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Meanwhile, the treatment-related AEs were dominated with lymphopenia, neutropenia and leukopenia, when the patients with HER2-negative locally advanced gastric cancer or cancer at the gastroesophageal junction were treated with combination of sintilimaband fluorouracil, leucovorin, oxaliplatin, or docetaxel \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Treating recurrent or metastatic cervical cancer with the combination of sintilimab andanrotinib, the predominant AEs were hypothyroidism, elevated aspartate aminotransferase levels, and hypertension \u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. These discrepancies in reported AE profiles across studies likely stem from sample size variations and differential concomitant medication use. Critically, our pharmacovigilance data suggest sintilimab\u0026rsquo;s organ-specific toxicity profile may be intrinsic to its mechanism that targeting immune checkpoints expressed across tissues rather than tumor-type dependent. Further mechanistic studies are essential to elucidate these etiologies and optimize risk mitigation strategies.\u003c/p\u003e\u003cp\u003eOur Preferred Term (PT) analysis identified myelosuppression, rash, and decreased white blood cell count as the most frequent adverse events, which are all immunologically mediated. This aligns with a recent a multicentre, open-label, parallel-group, randomised, controlled phase 3 trial data where most immune-related AEs were grade 1\u0026ndash;2 and rash predominated among grade 3\u0026ndash;4 immune-related AEs \u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. In this study, two fatal immune-related events (death, grade 5 AEs) were reported. Notably, hematologic toxicities like anemia and decreased white blood cel consistently emerge in sintilimab combination therapies, though their precise mechanistic relationship to PD-1 inhibition (versus chemotherapeutic effects) requires further investigation \u003csup\u003e\u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIt has been agreed that AEs such as myelosuppression and cytopenia are the side effects brought by chemotherapy \u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. Unexpectedly, increased myocardial necrosis markers ranked highest by ROR methodology, suggesting potential cardiotoxicity. Xu et al. conducted a phase III clinical trial in 650 patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma in 62 hospitals in China from 2019 to 2020 to compare the efficacy of sintilimab combined chemotherapy with placebo combined chemotherapy \u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. In this study, the incidence of cardiac treatment-related AEs in all grades in the sintilimab group was 10.7%, which was slightly higher than that in the placebo group (10.3%) \u003csup\u003e30\u003c/sup\u003e. Myocarditis occurred in one patient (0.3%), while heart failure promted sintilimab discontinuation in two others. Although the incidence of cardiac treatment-related AEs may be not high, the damage of important organs deserves vigilance. Future pharmacovigilance efforts should prioritize AE grading stratification alongside SOC/PT categorization to better inform risk-benefit assessments. This study establishes foundational real-world evidence for sintilimab's hematologic, dermatologic, and cardiac safety profiles to guide clinical decision-making.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eTo our knowledge, this study establishes the first systematic profile of sintilimab-associated AEs at SOC and PT levels using WHO-VigiAccess data. While providing critical real-world evidence to guide clinical risk assessment, these findings require further mechanistic research to elucidate sintilimab\u0026rsquo;s safety pathophysiology.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cb\u003eData collection.\u003c/b\u003e The pharmacovigilance data of sintilimab comes from the reports of WHO-VigiAccess database (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.vigiaccess.org\u003c/span\u003e\u003cspan address=\"https://www.vigiaccess.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) from 2020 to 2024. After identifying and deleting duplicate reports, 487 reports were finally included in the study. According to the SOC and PT of Medical Dictionary for Regulatory Activities (MedDRA), the data extracted from AE include patient demographic data, such as gender, age, reporting schedule, and geographical distribution. The final correlation AEs of sintilimab is identified according to SOC and PT levels.\u003c/p\u003e\u003cp\u003e\u003cb\u003eStatistical analysis.\u003c/b\u003e Disproportionality analysis was used to determine the potential correlation between sintilimab and AEs. These statistical methods include calculating reporting odds ratio (ROR) and the proportional reporting ratio (PRR). Specific calculation methods can refer to Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e. A retrospective quantitative approach was utilized in this study.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eTwo-by-two contingency table for disproportionality analysis.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eItem\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTarget adverse events reported\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eOther adverse events reported\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTarget drugs\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ea\u0026thinsp;+\u0026thinsp;b\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOther drugs\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ec\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ec\u0026thinsp;+\u0026thinsp;d\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ea\u0026thinsp;+\u0026thinsp;c\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eb\u0026thinsp;+\u0026thinsp;d\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ea\u0026thinsp;+\u0026thinsp;b\u0026thinsp;+\u0026thinsp;c\u0026thinsp;+\u0026thinsp;d\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eThe principles of disproportionate measurement and the criteria for signal detection.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMethod\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCalculation formula\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e໿Criteria\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eROR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\text{R}\\text{O}\\text{R}=\\frac{\\text{a}\\:/\\:\\text{c}}{b\\:/\\:d}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003ea\u0026thinsp;\u0026ge;\u0026thinsp;3\u003c/p\u003e\u003cp\u003eROR\u0026thinsp;\u0026ge;\u0026thinsp;1\u003c/p\u003e\u003cp\u003e95%CI (lower limit)\u0026thinsp;\u0026gt;\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:SE\\left(lnROR\\right)=\\sqrt{\\frac{1}{\\text{a}}+\\frac{1}{\\text{b}}+\\frac{1}{\\text{c}}+\\frac{1}{\\text{d}}}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:95\\%CI=\\:{\\text{e}}^{\\text{ln}\\left(ROR\\right)\\pm\\:1.96se}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e\u003cp\u003ePRR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\text{P}\\text{R}\\text{R}=\\frac{\\text{a}\\:/\\:(\\text{a}+\\text{b})}{c\\:/\\:(c+d)}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003ea\u0026thinsp;\u0026ge;\u0026thinsp;3\u003c/p\u003e\u003cp\u003ePRR\u0026thinsp;\u0026ge;\u0026thinsp;2\u003c/p\u003e\u003cp\u003e95%CI (lower limit)\u0026thinsp;\u0026gt;\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:SE\\left(lnPRR\\right)=\\sqrt{\\frac{1}{\\text{a}}-\\frac{1}{\\text{a}+\\text{b}}+\\frac{1}{\\text{c}}-\\frac{1}{\\text{c}+\\text{d}}}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:95\\%CI=\\:{\\text{e}}^{\\text{ln}\\left(PRR\\right)\\pm\\:1.96se}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{\\chi\\:}2\\:=\\frac{\\:{(\\text{a}\\text{d}-\\text{b}\\text{c})}^{2}(\\text{a}+\\text{b}+\\text{c}+\\text{d})}{(\\:\\text{a}+\\text{b})(\\text{a}+\\text{c})(\\text{c}+\\text{d})(\\text{b}+\\text{d})}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ea\u0026thinsp;\u0026ge;\u0026thinsp;3\u003c/p\u003e\u003cp\u003ePRR\u0026thinsp;\u0026ge;\u0026thinsp;2\u003c/p\u003e\u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{\\chi\\:}2\\ge\\:4\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:SE\\left(lnEBGM\\right)=\\sqrt{\\frac{1}{\\text{a}}+\\frac{1}{\\text{b}}+\\frac{1}{\\text{c}}+\\frac{1}{\\text{d}}}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:95\\%CI=\\:{\\text{e}}^{\\text{ln}\\left(EBGM\\right)\\pm\\:1.96se}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eCompeting interests\u003c/h2\u003e\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003cp\u003eNot applicable. The data used in this study came from the WHO VigiAccess Database so this study was deemed non-human subject related research.\u003c/p\u003e\u003ch2\u003eAI statement\u003c/h2\u003e\u003cp\u003eIn this study, DeepSeek was used to check for grammatical errors in the text, polish the language, but no DeepSeek was used for writing.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis work was supported by the 2022\u0026ndash;2023 Guangxi Zhuang Autonomous Region Health Commission Comprehensive Clinical Evaluation of Drugs Subject Funding Project (Project contract number: YPPJ005); Guangxi drug safety research project (Project number: [2024]010); and Hospital Pharmaceutical Research Project of Guangxi Pharmaceutical Society (Contract Number.: GXYXH-202403)\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eYoujia Guo, and Li Wen: Validation, Visualization, and Writing\u0026ndash;original draft; Fangcheng Jiang, Liling Pan, and Lei He: Data curation, Formal Analysis, and Methodology; Zhaoji Liu, and Qiong Wu: Data curation, and Formal Analysis; Zefeng Lai: Supervision, Validation, and Writing-review and editing; Qichun Huang, and Yan Li: Conceptualization, Funding acquisition, Project administration, Supervision, Validation, and Writing-review and editing.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe original data for this article were obtained from the VigiAccess website and can be shared with investigators.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eZhou C, Wu L, Fan Y, et al. Sintilimab Plus Platinum and Gemcitabine as First-Line Treatment for Advanced or Metastatic Squamous NSCLC: Results From a Randomized, Double-Blind, Phase 3 Trial (ORIENT-12). J Thorac Oncol Sep. 2021;16(9):1501\u0026ndash;11. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jtho.2021.04.011\u003c/span\u003e\u003cspan address=\"10.1016/j.jtho.2021.04.011\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSiegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin Jan-Feb. 2025;75(1):10\u0026ndash;45. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3322/caac.21871\u003c/span\u003e\u003cspan address=\"10.3322/caac.21871\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin May-Jun. 2024;74(3):229\u0026ndash;63. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3322/caac.21834\u003c/span\u003e\u003cspan address=\"10.3322/caac.21834\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang C, Sun YX, Yi DC, et al. Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant NSCLC: Phase 2 trial interim results (NEOTIDE/CTONG2104). Cell Rep Med Jul. 2024;16(7):101615. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.xcrm.2024.101615\u003c/span\u003e\u003cspan address=\"10.1016/j.xcrm.2024.101615\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLi Y, Liang X, Li H, Chen X. Efficacy and safety of immune checkpoint inhibitors for advanced non-small cell lung cancer with or without PD-L1 selection: A systematic review and network meta-analysis. Chin Med J (Engl) Sep. 2023;20(18):2156\u0026ndash;65. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/cm9.0000000000002750\u003c/span\u003e\u003cspan address=\"10.1097/cm9.0000000000002750\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShi Y, Wu L, Yu X, et al. Sintilimab versus docetaxel as second-line treatment in advanced or metastatic squamous non-small-cell lung cancer: an open-label, randomized controlled phase 3 trial (ORIENT-3). Cancer Commun (Lond) Dec. 2022;42(12):1314\u0026ndash;30. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/cac2.12385\u003c/span\u003e\u003cspan address=\"10.1002/cac2.12385\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYang Y, Wang Z, Fang J, et al. Efficacy and Safety of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC: a Randomized, Double-Blind, Phase 3 Study (Oncology pRogram by InnovENT anti-PD-1-11). J Thorac Oncol Oct. 2020;15(10):1636\u0026ndash;46. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jtho.2020.07.014\u003c/span\u003e\u003cspan address=\"10.1016/j.jtho.2020.07.014\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYang Y, Sun J, Wang Z, et al. Updated Overall Survival Data and Predictive Biomarkers of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC in the Phase 3 ORIENT-11 Study. J Thorac Oncol Dec. 2021;16(12):2109\u0026ndash;20. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jtho.2021.07.015\u003c/span\u003e\u003cspan address=\"10.1016/j.jtho.2021.07.015\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLu S, Wu L, Jian H, et al. Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): first interim results from a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol Sep. 2022;23(9):1167\u0026ndash;79. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s1470-2045(22)00382-5\u003c/span\u003e\u003cspan address=\"10.1016/s1470-2045(22)00382-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGao Z, Teng J, Qiao R, et al. Efficacy and Safety of a Therapy Combining Sintilimab and Chemotherapy With Cryoablation in the First-Line Treatment of Advanced Nonsquamous Non-Small Cell Lung Cancer: Protocol for a Phase II, Pilot, Single-Arm, Single-Center Study. JMIR Res Protoc Nov. 2024;8:13:e64950. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2196/64950\u003c/span\u003e\u003cspan address=\"10.2196/64950\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNi J, Wang X, Wu L, et al. Sintilimab in combination with stereotactic body radiotherapy and granulocyte-macrophage colony-stimulating factor in metastatic non-small cell lung cancer: The multicenter SWORD phase 2 trial. Nat Commun Aug. 2024;22(1):7242. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41467-024-51807-7\u003c/span\u003e\u003cspan address=\"10.1038/s41467-024-51807-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhou X, Zhou L, Yao Z, et al. Safety and Tolerability of Low-Dose Radiation and Stereotactic Body Radiotherapy\u0026thinsp;+\u0026thinsp;Sintilimab for Treatment-Na\u0026iuml;ve Stage IV PD-L1\u0026thinsp;+\u0026thinsp;Non-Small Cell Lung Cancer Patients. Clin Cancer Res Oct. 2023;13(20):4098\u0026ndash;108. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1158/1078-0432.Ccr-23-0315\u003c/span\u003e\u003cspan address=\"10.1158/1078-0432.Ccr-23-0315\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCappuyns S, Corbett V, Yarchoan M, Finn RS, Llovet JM. Critical Appraisal of Guideline Recommendations on Systemic Therapies for Advanced Hepatocellular Carcinoma: A Review. JAMA Oncol. Mar 2024;1(3):395\u0026ndash;404. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamaoncol.2023.2677\u003c/span\u003e\u003cspan address=\"10.1001/jamaoncol.2023.2677\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFulgenzi CAM, D'Alessio A, Airoldi C, et al. Comparative efficacy of novel combination strategies for unresectable hepatocellular carcinoma: A network metanalysis of phase III trials. Eur J Cancer Oct. 2022;174:57\u0026ndash;67. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ejca.2022.06.058\u003c/span\u003e\u003cspan address=\"10.1016/j.ejca.2022.06.058\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu L, Bai H, Wang C, et al. Efficacy and Safety of First-Line Immunotherapy Combinations for Advanced NSCLC: A Systematic Review and Network Meta-Analysis. J Thorac Oncol Jul. 2021;16(7):1099\u0026ndash;117. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jtho.2021.03.016\u003c/span\u003e\u003cspan address=\"10.1016/j.jtho.2021.03.016\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGao S, Li N, Gao S, et al. Neoadjuvant PD-1 inhibitor (Sintilimab) in NSCLC. J Thorac Oncol May. 2020;15(5):816\u0026ndash;26. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jtho.2020.01.017\u003c/span\u003e\u003cspan address=\"10.1016/j.jtho.2020.01.017\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMaggie Liu SY, Huang J, Deng JY, et al. PD-L1 expression guidance on sintilimab versus pembrolizumab with or without platinum-doublet chemotherapy in untreated patients with advanced non-small cell lung cancer (CTONG1901): A phase 2, randomized, controlled trial. Sci Bull (Beijing) Feb. 2024;26(4):535\u0026ndash;43. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.scib.2023.12.046\u003c/span\u003e\u003cspan address=\"10.1016/j.scib.2023.12.046\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiang Q, Liao X, Huang Y et al. Safety study on adverse events of zanubrutinib based on WHO-VigiAccess and FAERS databases. Expert Opin Drug Saf Oct 15 2024:1\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/14740338.2024.2416917\u003c/span\u003e\u003cspan address=\"10.1080/14740338.2024.2416917\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhou Q, Xie Q, Liu Q, et al. DNA methylation inhibitors adverse reaction characteristic analysis: a descriptive analysis from WHO-VigiAccess. Front Pharmacol. 2024;15:1470148. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fphar.2024.1470148\u003c/span\u003e\u003cspan address=\"10.3389/fphar.2024.1470148\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang P, Dai J, Sun F, et al. Neoadjuvant Sintilimab and Chemotherapy for Resectable Stage IIIA Non-Small Cell Lung Cancer. Ann Thorac Surg Sep. 2022;114(3):949\u0026ndash;58. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.athoracsur.2022.01.039\u003c/span\u003e\u003cspan address=\"10.1016/j.athoracsur.2022.01.039\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLi N, Li Z, Fu Q, et al. Efficacy and safety of neoadjuvant sintilimab in combination with FLOT chemotherapy in patients with HER2-negative locally advanced gastric or gastroesophageal junction adenocarcinoma: an investigator-initiated, single-arm, open-label, phase II study. Int J Surg Apr. 2024;1(4):2071\u0026ndash;84. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/js9.0000000000001119\u003c/span\u003e\u003cspan address=\"10.1097/js9.0000000000001119\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXu Q, Wang J, Sun Y, et al. Efficacy and Safety of Sintilimab Plus Anlotinib for PD-L1-Positive Recurrent or Metastatic Cervical Cancer: A Multicenter, Single-Arm, Prospective Phase II Trial. J Clin Oncol Jun. 2022;1(16):1795\u0026ndash;805. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1200/jco.21.02091\u003c/span\u003e\u003cspan address=\"10.1200/jco.21.02091\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu X, Zhang Y, Yang KY, et al. Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial. Lancet Jun. 2024;22(10445):2720\u0026ndash;31. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s0140-6736(24)00594-4\u003c/span\u003e\u003cspan address=\"10.1016/s0140-6736(24)00594-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJiang H, Yu X, Li N, et al. Efficacy and safety of neoadjuvant sintilimab, oxaliplatin and capecitabine in patients with locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma: early results of a phase 2 study. J Immunother Cancer Mar. 2022;10(3). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/jitc-2021-003635\u003c/span\u003e\u003cspan address=\"10.1136/jitc-2021-003635\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang Y, Zhao J, Liang H, et al. Efficacy and safety of sintilimab plus albumin-bound-paclitaxel in recurrent or metastatic cervical cancer: a multicenter, open-label, single-arm, phase II trial. EClinicalMedicine Nov. 2023;65:102274. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.eclinm.2023.102274\u003c/span\u003e\u003cspan address=\"10.1016/j.eclinm.2023.102274\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eQue Y, Wang J, Sun F, et al. Safety and clinical efficacy of sintilimab (anti-PD-1) in pediatric patients with advanced or recurrent malignancies in a phase I study. Signal Transduct Target Ther Oct. 2023;13(1):392. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41392-023-01636-9\u003c/span\u003e\u003cspan address=\"10.1038/s41392-023-01636-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang QL, Wu TT, Han Y, Zheng ZM, Zhang Y. Chemotherapy-Induced Myelosuppression in Esophageal Cancer Patients: Risks and Suggestions for Its Management. Curr Med Sci Jun. 2022;42(3):530\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s11596-022-2587-3\u003c/span\u003e\u003cspan address=\"10.1007/s11596-022-2587-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBoccia R, Glaspy J, Crawford J, Aapro M. Chemotherapy-Induced Neutropenia and Febrile Neutropenia in the US: A Beast of Burden That Needs to Be Tamed? \u003cem\u003eOncologist\u003c/em\u003e. Aug. 2022;5(8):625\u0026ndash;36. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/oncolo/oyac074\u003c/span\u003e\u003cspan address=\"10.1093/oncolo/oyac074\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXu J, Jiang H, Pan Y, et al. Sintilimab Plus Chemotherapy for Unresectable Gastric or Gastroesophageal Junction Cancer: The ORIENT-16 Randomized Clinical Trial. Jama Dec. 2023;5(21):2064\u0026ndash;74. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jama.2023.19918\u003c/span\u003e\u003cspan address=\"10.1001/jama.2023.19918\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXu J, Sintilimab, Toxicity-Reply C. \u003cem\u003eJama\u003c/em\u003e. Apr 16 2024;331(15):1334\u0026ndash;1335. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jama.2024.0676\u003c/span\u003e\u003cspan address=\"10.1001/jama.2024.0676\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pharmacology-and-toxicology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"phat","sideBox":"Learn more about [BMC Pharmacology and Toxicology](http://bmcpharmacoltoxicol.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/phat/Default.aspx","title":"BMC Pharmacology and Toxicology","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Sintilimab, adverse event, real‑world pharmacovigilance study, WHO-VigiAccess database","lastPublishedDoi":"10.21203/rs.3.rs-7907424/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7907424/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eSintilimab, a high-affinity PD-1 inhibitor, blocks the interaction between PD-1 and PD-L1 to restore T-cell function. Clinically used with chemotherapy for cancers like non-small cell lung carcinoma and hepatocellular carcinoma, its adverse event (AE) profile remains critical. Here we conducted the pharmacovigilance analysis of sintilimab-associated AEs using the WHO VigiAccess database. Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) were used to detect the risk signals, characterizing AE distribution at System Organ Class (SOC) and Preferred Term (PT) levels. Our analysis reveals hematologic toxicity as the predominant SOC-level AE. At the PT level, myelosuppression was the most frequently reported event. To our knowledge, these findings provide the first evidence from real-world global safety data on sintilimab\u0026rsquo;s AEs, and may enhance clinical monitoring and risk mitigation strategies for sintilimab therapy.\u003c/p\u003e","manuscriptTitle":"Sintilimab Pharmacovigilance in Real-World Practice: Analysis Utilizing the WHO VigiAccess Database","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-25 15:50:40","doi":"10.21203/rs.3.rs-7907424/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"288333388885551922932953547485020933933","date":"2025-11-14T14:39:29+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-14T12:17:03+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-10-22T16:00:11+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-22T01:46:36+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-22T01:46:07+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pharmacology and Toxicology","date":"2025-10-20T15:57:36+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pharmacology-and-toxicology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"phat","sideBox":"Learn more about [BMC Pharmacology and Toxicology](http://bmcpharmacoltoxicol.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/phat/Default.aspx","title":"BMC Pharmacology and Toxicology","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"acbed027-4423-4045-8f15-95f73e414ea8","owner":[],"postedDate":"November 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-11-25T15:50:40+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-25 15:50:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7907424","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7907424","identity":"rs-7907424","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}