Real-world pharmacovigilance study of voclosporin based on FAERS and VigiBase

Real-world pharmacovigilance study of voclosporin based on FAERS and VigiBase | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 29 July 2025 V1 Latest version Share on Real-world pharmacovigilance study of voclosporin based on FAERS and VigiBase Authors : Jingjing Wang , Yongli Yang , xiaobo chen , Yi Zhang , Xue Yang , Ying Qiao , Xudong Xia 0009-0008-0543-4947 , and Xiaocan Jia 0000-0003-0895-2957 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.175381768.85031512/v1 181 views 130 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background The safety evaluations of voclosporin in the real world are lacking while it is increasingly used in clinical practice. This study aimed to investigate the safety of voclosporin to enhance the rational and safe clinical use. Methods Data was collected in the Food and Drug Administration Adverse Event Reporting System (FAERS) and the World Health Organization international pharmacovigilance database (VigiBase). Disproportionality analysis including reporting odds ratio (ROR) and Medicines and Healthcare Products Regulatory Agency (MHRA) method adjusted the detection criteria for the proportional reporting ratio (PRR) was employed to identify potential safety signals associated with voclosporin. Results The system organ class commonly involved in AEs was gastrointestinal disease and general disorders and administration site conditions both in FAERS and VigiBase database. Compared with all other drugs, therapy interrupted (ROR=23.14, PRR=21.98, χ 2 =14,291.52) was identified as the most prevalent positive signal. Urine protein/creatinine ratio increased (ROR=431.09, PRR=427.27, χ 2 =39,390.40) was the strongest positive signal. Moreover, some priority AEs were detected compared with other calcineurin inhibitors (CNIs), such as joint stiffness (ROR=21.11, PRR=21.10, χ 2 =32.40) and hypersomnia (ROR=19.19, PRR=19.18, χ 2 =28.72). A total of 11 potential AEs not listed in the voclosporin labeling were identified, with the most significant positive signals being menstrual disorder (ROR=7.65, PRR=7.65, χ 2 =57.47). Conclusion When prescribing voclosporin, clinicians should be alert AEs related to gastrointestinal disease and general disorders and administration site conditions, as well as serious AEs involving the renal disorders. Especially, more attention should be paid to newly identified AEs such as menstrual disorder and blood urine present. Title page Article title： Real-world pharmacovigilance study of voclosporin based on FAERS and VigiBase Author names： Jingjing Wang 1 , Yongli Yang 1 , Xiaobo Chen 2 , Yi Zhang 1 , Xue Yang 2 , Ying Qiao 1 , Xudong Xia 1, 2* , Xiaocan Jia 1* 1 Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China. 2 Center for Drug Evaluation of Henan, Zhengzhou 450000, Henan, China. *Corresponding Author: Xiaocan Jia, MD, College of Public Health, Zhengzhou University, No.100 Science Avenue, Zhengzhou, email: [email protected] . Xudong Xia, MM, College of Public Health, Zhengzhou University and Center for Drug Evaluation of Henan, No.100 Science Avenue and No.127 Garden Road, Zhengzhou, email: [email protected] . Xiaocan Jia and Xudong Xia have contributed equally to the writing and revision of the manuscript. Keywords voclosporin; lupus nephritis; pharmacovigilance; disproportionality analysis; FAERS, VigiBase Word count:2559; table count: 4; figure count:3 Abstract Background The safety evaluations of voclosporin in the real world are lacking while it is increasingly used in clinical practice. This study aimed to investigate the safety of voclosporin to enhance the rational and safe clinical use. Methods Data was collected in the Food and Drug Administration Adverse Event Reporting System (FAERS) and the World Health Organization international pharmacovigilance database (VigiBase). Disproportionality analysis including reporting odds ratio (ROR) and Medicines and Healthcare Products Regulatory Agency (MHRA) method adjusted the detection criteria for the proportional reporting ratio (PRR) was employed to identify potential safety signals associated with voclosporin. Results The system organ class commonly involved in AEs was gastrointestinal disease and general disorders and administration site conditions both in FAERS and VigiBase database. Compared with all other drugs, therapy interrupted (ROR=23.14, PRR=21.98, χ 2 =14,291.52) was identified as the most prevalent positive signal. Urine protein/creatinine ratio increased (ROR=431.09, PRR=427.27, χ 2 =39,390.40) was the strongest positive signal. Moreover, some priority AEs were detected compared with other calcineurin inhibitors (CNIs), such as joint stiffness (ROR=21.11, PRR=21.10, χ 2 =32.40) and hypersomnia (ROR=19.19, PRR=19.18, χ 2 =28.72). A total of 11 potential AEs not listed in the voclosporin labeling were identified, with the most significant positive signals being menstrual disorder (ROR=7.65, PRR=7.65, χ 2 =57.47). Conclusion When prescribing voclosporin, clinicians should be alert AEs related to gastrointestinal disease and general disorders and administration site conditions, as well as serious AEs involving the renal disorders. Especially, more attention should be paid to newly identified AEs such as menstrual disorder and blood urine present. Introduction Lupus nephritis (LN) was one of the most severe manifestations of systemic lupus erythematosus (SLE) and a major cause of mortality [1, 2]. The worldwide incidence of SLE was estimated to be 5.14 per 100,000 person-years and the prevalence would be 43.7 per 100,000 individuals [3]. Approximately 45% of patients with SLE would experience LN during the course of their disease, and 10–30% of those with LN would develop end-stage renal disease [4, 5]. Mycophenolate mofetil (MMF) or cyclophosphamide coadministered with glucocorticoids as initial treatments for active LN, appeared to be inadequate [6, 7]. These results highlight the necessity for more effective LN therapies. Voclosporin, the first oral therapy, was a novel calcineurin inhibitor (CNI) approved by the Food and Drug Administration (FDA) for the treatment of LN in 2021. Like other CNIs, voclosporin exerted its action by blocking the activation of T-cell-specific transcription factors such as the nuclear factor of activated T cells [8]. Multiple clinical trials have demonstrated the safety and efficacy of voclosporin in patients with LN. During the study period, a significantly higher proportion of patients in the voclosporin group (41%) than in the placebo group (23%) had a complete renal response. More than 85% of the voclosporin arm experienced adverse events (AEs), with serious AEs observed in approximately 18% [9, 10]. However, limitations on the number of research units and the duration of research might lead to omission of serious or long-term AEs[11]. The safety evaluations of voclosporin in the real world are lacking while it is increasingly used in clinical practice. The FDA Adverse Event Reporting System (FAERS) and the World Health Organisation (WHO) global individual case safety reports database (VigiBase) are spontaneous database. They offer real-world AE data from global populations, potentially highlighting issues that may be overlooked in controlled clinical trials. Therefore, the safety of voclosporin was investigated in this study using FAERS and VigiBase database and compared with other CNIs, to provide additional evidence for its rational and safe clinical use. Methods Data source In this study, we collected AE reports associated with voclosporin from the first quarter of 2021 (Q1) to the third quarter of 2024 (Q3) from FAERS database (https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html) to perform the pharmacovigilance analysis. Furthermore, AE reports in the World Health Organization international pharmacovigilance database (VigiBase) up to June 15, 2025 were extracted. Data processing procedure The FAERS database contains demographic information, drug information, AE information, patient outcomes, report sources, therapy start and end dates and drug indications. Before analysis, a deduplication procedure was performed according to the FDA’s recommendations. For the same CASEID report, the largest FDA_DT was retained, followed by the selection of the largest PRIMARYID where the CASEID and FDA_DT were identical. Generic name (voclosporin) and brand name (lupkynis) were applied to identify AE reports related to voclosporin. To enhance accuracy, AE reports where the ‘role_cod’ column indicated voclosporin as the ‘primary suspected (PS)’ drug were selected. The AEs in the FAERS database were standardized using the preferred term (PT) and system organ class (SOC) according to the Medical Dictionary for Regulatory Activities (MedDRA27.0). The flowchart of AEs analysis process for voclosporin was shown in Supplementary Figure S1. Statistical analysis Disproportionality analysis including reporting odds ratio (ROR) and Medicines and Healthcare products Regulatory Agency (MHRA) method was employed to identify potential safety signals associated with voclosporin [12, 13]. MHRA has adjusted the detection criteria for the proportional reporting ratio (PRR) and incorporated the chi-square (χ 2 ) value as a condition for signal generation[14]. Serious outcomes refer to one or more of the following outcomes were documented including death, hospitalization, life-threatening, disability, and other serious outcomes. To reduce the likelihood of false positives, at least 10 reported AEs were selected based on relevant pharmacovigilance articles. Fourfold table of the disproportionality analysis was shown in Supplementary Table S1. Supplementary Table S2 listed the specific algorithm and criteria. In this study, the detection of an AE positive signal depended on its simultaneous alignment with two algorithm criteria. To provide a more comprehensive assessment of voclosporin, two control groups were chosen. Firstly, we calculated AE signals compared with all other drugs. Secondly, the same disproportionality analysis was conducted using other calcineurin inhibitors (Anatomical Therapeutic Classification L04AD) as the control group. The Weibull distribution analysis was applied to model changes in the incidence of AEs over time. The shape of the Weibull distribution was described by the scale (α) and shape (β) parameters. Shape parameters β value and 95% CI were less than 1, suggesting had an early failure type. Shape parameters β value is equal to or close to 1 and 95% CI contains 1, suggesting had a random failure type. Shape parameters β value and 95% CI were greater than 1, suggesting had a wear-off type[15]. To identify reports of suspected adverse drug reactions that deserve special attention, the European Medicines Agency has developed the designated medical event (DME) list, which includes 62 PTs. In this study, the screening process aimed to identify valuable signals related to voclosporin based on the DME list. Subsequently, the SOC corresponding to each PT was queried for a more targeted and in-depth analysis. All statistical analyses were performed using SAS 9.4 and R 4.4.1 software. Results Descriptive analysis During the study period, a total of 4,986 reports concerning voclosporin were obtained from the FAERS database ( Table1) . The number of female patients was significantly higher than male patients, with a female-to-male ratio of 5.46:1. The major voclosporin-related AE reports were observed in adult patients, accounting for 36.08%. The proportion of serious outcome was 24.90%. The AE reports were submitted by consumers and health professional, accounting for 92.46% of the total number of reported figures. Most AE reports originated from the U.S. There were 5,925 reports on voclosporin from the VigiBase database ( TableS3 ). Similarly, the number of reports involving female patients is higher, with a female-to-male ratio of 5.24:1. The highest percentage of AE reports was observed among adults, accounting for 35.00%. These AE reports exclusively occurred in the Americas and Europe, with the majority originating from the Americas. The number of reports of AEs related to voclosporin has increased year by year both in FAERS and VigiBase database. Death cases analysis In FAERS database, there were 30 fatal cases, 25 cases occurred in female patients ( Supplementary Table S4 ). A total of 16 cases occurred in adult patients. Co-medication was observed in fifty percent of the cases. Deaths were more frequently observed at higher doses of the drug. The highest proportion of death-related AEs involving SOC was general disorders and administration site conditions, involving PTs including decreased appetite, pneumonia, sepsis and so on. Signal detection at the SOCs level AE reports related to voclosporin accrued 13,856 AEs, involving 27 SOCs in the FAERS database as shown in Figure1 A . Gastrointestinal disorders were the SOC with the highest number of reported cases. Positive signals were identified for surgical and medical procedures (ROR=4.19, PRR=4.00, χ 2 =1,887.52), renal and urinary disorders (ROR=3.04, PRR=2.94, χ 2 =918.82) and vascular disorders (ROR=2.46, PRR=2.40, χ 2 =499.78). In the VigiBase database, there were 12,598 AEs associated with voclosporin, involving 27 SOCs (Figure1 B) . General disorders and administration site conditions was the SOC with the highest number of reported cases, followed by Gastrointestinal disorders. Signal detection at the PTs level There were 1,180 PTs were found to be associated with voclosporin in the FAERS database. Some AEs that were unrelated to the drug itself have been excluded, such as product dose omission issue, product packaging difficult to open. Eventually, a total of 72 positive PT signals were confirmed related to voclosporin ( Table2 and Supplementary Table S5) . The most commonly reported AE was therapy interrupted, followed by hypertension. Urine protein/creatinine ratio increased was the strongest positive signal sorted by ROR. Moreover, a total of 11 potential AEs not listed in the voclosporin labeling were identified, encompassing 6 SOCs ( Supplementary Table S6) . Among these, general disorders and administration site conditions was the most prevalent. Results of time to onset and Weibull distribution analysis suggested that peripheral swelling and joint swelling had early failure types (Supplementary Table S7 ). Signal detection compared with other CNIs In the FAERS database, when compared with other CNIs, at the SOCs level, both surgical and medical procedures and general disorders and vascular disorders were significant ( Supplemental Table S8 ). At the PTs level, urine abnormality was the strongest signal. Notably, there were several distinct positive signals, such as joint stiffness and drowsiness, when compared to the results of the control group with all other drugs (Table3) . Time to onset analysis Among all reported AEs, a total of 1,399 events provided comprehensive and precise information regarding the time of occurrence in the FAERS database. As illustrated in Figure2 and Table4 , the majority of AE reports occurred within the first month following the initiation of voclosporin, and analysis using the Weibull distribution indicated an early failure type. DME list analysis Twelve of the 1,180 PT signals matched the DME list, as shown in Figure3 . The highest number of reports was for acute kidney injury, followed by renal failure. These signals mainly focus on renal and urinary disorders. Discussion This study provided the first comprehensive evaluation of the safety of voclosporin utilizing the FAERS and the VigiBase database. In both databases, the SOC commonly involved in AE were gastrointestinal disease and general disorders and administration site conditions. When compared with all other drugs, therapy interrupted was identified as the most prevalent positive AE signal. Urine protein/creatinine ratio increased was the strongest positive AE signal. Moreover, some priority AEs were detected compared with other CNIs, such as joint stiffness and hypersomnia. A total of 11 potential AEs not listed in the voclosporin labeling were identified, such as gingival swelling. Compared to all other drugs, the most common AE was gastrointestinal disorders at the SOC level. Voclosporin, as a CNI, could disrupt the balance of gut microbiota, leading to dysbiosis and gastrointestinal issues such as diarrhea [16]. Renal and urinary disorders and vascular disorders were identified as positive SOC signals. In addition, renal adverse effects should also be given special attention according to the DME list. Like other CNIs nephrotoxicity, acute nephrotoxicity was primarily caused by vasoconstriction of the afferent glomerular arterioles[17]. Chronic nephrotoxicity, characterized by a progressive loss in glomerular and tubular function, had a more complex pathogenesis[18]. Nephrotoxicity might be related to the dosage of voclosporin, particularly at higher doses exceeding 0.80 mg/kg [8]. Hypertension was a well-known AE of voclosporin in the vascular disorders. This might be attributed to the activation of the sodium–chloride cotransporter in the distal convoluted tubule to salt-sensitive hypertension. Additionally, voclosporin increased plasma renin concentration, which likely contributed to the development of hypertension via angiotensin II [19]. At the PT level, therapy interrupted was the most common positive signal. It was attributed to any of the following AEs associated with voclosporin: a decrease in estimated glomerular filtration rate (eGFR) from baseline, appearance of neurotoxicity, pure red cell aplasia, or increases in blood pressure that cannot be managed [10]. The urine protein/creatinine ratio increased was the strongest positive signal, usually indicating the presence of urinary protein in the urine. It might be related to a decrease in eGFR or the progression of LN [20]. CNIs resulted in a hemodynamically mediated decrease in eGFR, which occurred through dose-dependent vasoconstriction within the nephron[21]. Compared to other CNIs, joint stiffness, hypersomnia, neck pain, ear infection should be priority AEs. Joint involvement was a common presenting symptom in patients with SLE, and up to 90% of patients would have musculoskeletal symptoms during the course of the disease [22]. Hypersomnia was classified as a nervous system disorder, has been reported in other CNIs[23]. Because calcineurin was abundant in the brain, its inhibition could form the basis for the pathophysiology of neurotoxicity observed in patients on calcineurin inhibitor therapy[24].In addition, the instructions of drug indicate that an accidental overdose may result in hypersomnia. Immunosuppressants, including voclosporin, increased the risk of developing bacterial, viral, fungal, and protozoal infection. This is a result of voclosporin decreased the activity of immune system[25]. There were several new AE signals that were not included in the voclosporin instructions, including menstrual disorder, blood urine present, swelling face, peripheral swelling, generalised oedema, oedema, fluid retention, gout, heavy menstrual bleeding, pollakiuria, joint swelling and muscle spasms. The result might be attributed to the fact that a broader and more diverse population in real-world usage, and that drug-drug interactions were more common in everyday clinical settings[26]. Ovulation could be considered an inflammatory process in which cells of the immune system would participate. Voclosporin as an immunosuppressive drug could impact ovulation, leading to irregular menstruation[27]. The underlying mechanism of some new AE signal remains unclear, but they did not preclude disease progression in patients with LN during the treatment period. Blood urine present might be attributed to the glomerular deposition of immune complexed with subsequent release of inflammatory cytokines and activation of the complement cascade. This process resulted in glomerular capillary injury and passage of red blood cells into the urinary space[28]. Inflammation can lead to kidney damage often results in significant edema or swelling due to fluid retention. These findings served as a warning for us to pay close attention to these new AE signals associated with voclosporin and emphasized the necessity of continuous monitoring of drug-related AEs. Several inherent limitations of this study are unavoidable. Firstly, the absence of a total population size for voclosporin use, along with multiple underlying confounders. Therefore, the incidence of AEs cannot be proven. Secondly, considering the relatively short time that voclosporin has been on the market and AE reports primarily originating from the U.S., the current conclusions may be affected by the limited number and race of reported cases. Finally, the new AE signals identified in this study associated with voclosporin require prospective observations for confirmation. Conclusion The AEs associated with voclosporin found in this retrospective analysis based on FAERS and VigiBase were generally consistent with those listed in the product labels. When prescribing voclosporin, clinicians should be alert AEs related to gastrointestinal disease and general disorders and administration site conditions, as well as serious AEs involving the renal and urinary disorders. Especially, more attention should be paid to newly identified AEs, including menstrual disorder, blood urine present and swelling face, and so on. In summary, our findings could enhance awareness of voclosporin-related toxicities, promoting its rational use in clinical practice. Acknowledgements We acknowledge the FAERS, which provided and gave permission to use the data analyzed in the present study. Declaration of interests All authors declare that they have no competing interests. Funding This work was supported by the Soft Science Project of Henan Province (Project Number: 242400410362). Data sharing statement All data generated or analyzed during this study are included in this published article and its supplementary files. ICI reports are available and can be retrieved form the FAERS Publish Dashboard Author contributions Jingjing Wang drafted the initial manuscript. Yongli Yang contributed to the design of study. Xiaobo Chen performed the manuscript. Yi Zhang and Xue Yang assisted in analyzing the data. Xiaocan Jia and Xudong Xia were involved in study supervision. All authors read and approved the final version of the manuscript. Ethics The FAERS database is accessible to the public and patient records are anonymized and de-identified. Ethical clearance and informed consent are not required for this study. References 1. Uzzo M, Schumacher H, Steffgen J, Deutschel S, Jayne D, Bajema I. Outcome of lupus nephritis patients treated with an anti-CD40 monoclonal antibody according to kidney biopsy features. In: Arthritis Rheumatol, 20241208 Edition, 2024.2. Fava A, Wagner CA, Guthridge CJ, Kheir J, Macwana S, DeJager W, Gross T, Izmirly P, Belmont HM, Diamond B, Davidson A, Utz PJ, Weisman MH, Magder LS, Guthridge JM, Petri M, Buyon J, James JA. Association of Autoantibody Concentrations and Trajectories With Lupus Nephritis Histologic Features and Treatment Response. Arthritis Rheumatol 2024; 76: 1611-22.3. Roveta A, Parodi EL, Brezzi B, Tunesi F, Zanetti V, Merlotti G, Francese A, Maconi AG, Quaglia M. 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Gender Female 4168 84.51 Male 763 15.47 Missing 55 1.03 Age (years) <18 26 0.52 18-64 1799 36.08 ≥65 92 1.85 Missing 3069 61.55 Serious outcome Hospitalization 479 38.10 Death 30 2.39 Disability 1 0.08 Life-threatening 1 0.08 Other serious outcomes 746 59.35 Reporting country United States 4979 99.86 Non-United States 7 0.14 Reporter Consumer 4201 84.26 Health professional 409 8.20 Physician 354 7.10 Pharmacist 22 0.44 Reporting year 2024(Q3) 2054 41.20 2023 1429 28.66 2022 1158 23.23 2021 345 6.92 Table2 Top30 signal strength of voclosporin compared with all other drugs ranked by ROR at the PTs level from FAERS. Urine protein/creatinine ratio increased 123 431.09(351.42-528.83) 427.27 39,390.40 Complement factor C3 decreased 11 270.58(141.31-518.10) 270.36 2,444.67 Double stranded DNA antibody positive 14 177.24(101.39-309.84) 177.06 2,157.68 Proteinuria 250 59.35(52.23-67.45) 58.30 13,480.63 Glomerular filtration rate decreased 161 53.52(45.68-62.71) 52.91 7,881.08 Urine albumin/creatinine ratio increased 10 79.49(41.97-150.54) 79.43 729.93 Protein total increased 22 40.20(26.29-61.46) 40.14 814.52 Protein urine present 37 30.43(21.96-42.17) 30.35 1,026.41 Therapy interrupted 724 23.14(21.45-24.95) 21.98 14,291.52 Urine abnormality 28 24.51(16.86-35.64) 24.46 618.55 Glomerular filtration rate abnormal 14 26.46(15.58-44.92) 26.43 335.76 Lupus nephritis 12 23.85(13.47-42.22) 23.83 257.75 Hair growth abnormal 21 17.77(11.55-27.34) 17.74 327.31 Blood creatinine abnormal 15 19.03(11.43-31.69) 19.01 252.24 Laboratory test abnormal 88 14.03(11.36-17.32) 13.95 1,046.82 Blood creatinine increased 157 12.64(10.79-14.80) 12.51 1,647.89 Hypertension 489 11.11(10.15-12.16) 10.75 4,304.91 Systemic lupus erythematosus 120 10.99(9.18-13.16) 10.90 1,071.29 Gingival swelling 10 14.50(7.77-27.05) 14.49 124.22 Blood creatine increased 12 12.53(7.09-22.12) 12.52 125.94 Renal impairment 143 7.22(6.12-8.52) 7.15 754.07 Blood potassium increased 24 8.45(5.65-12.63) 8.44 156.33 Blood pressure abnormal 36 7.03(5.07-9.76) 7.02 184.86 Abdominal discomfort 213 5.33(4.65-6.11) 5.26 734.94 Blood pressure increased 195 5.34(4.63-6.15) 5.28 675.21 Abdominal pain upper 212 5.25(4.58-6.01) 5.18 714.42 Menstrual disorder* 10 7.65(4.11-14.25) 7.65 57.47 Therapy cessation 57 5.31(4.09-6.89) 5.29 197.66 Dyspepsia 87 4.67(3.78-5.77) 4.65 248.69 Renal pain 14 6.15(3.64-10.40) 6.14 60.00 PT: preferred term; N: number of adverse events; ROR: reporting odds ratio; 95% CI, 95% confidence interval; PRR: proportional reporting ratio; *: the instruction does not mention. Table3 Top 30 signal strength of voclosporin compared with other CNIs ranked by ROR at the PTs level from FAERS. Urine abnormality 28 107.62(14.64-791.04) 107.40 101.82 Heavy menstrual bleeding 14 53.75(7.07-408.83) 53.70 48.28 Flank pain 10 38.38(4.91-299.89) 38.36 33.08 Glomerular filtration rate decreased 161 36.74(22.28-60.59) 36.33 529.65 Gastroenteritis viral 17 32.64(7.54-141.31) 32.60 54.84 Frequent bowel movements 16 30.72(7.06-133.63) 30.69 51.07 Blood pressure abnormal 36 27.69(10.86-70.57) 27.62 112.69 Brain fog 13 24.95(5.63-110.60) 24.93 39.83 Retching 13 24.95(5.63-110.60) 24.93 39.83 Protein urine present 37 23.71(10.01-56.20) 23.65 112.08 Joint swelling* 67 21.52(11.64-39.78) 21.42 198.31 Nasopharyngitis 94 21.35(12.73-35.80) 21.21 277.68 Joint stiffness * 11 21.11(4.68-95.26) 21.10 32.40 Hypersomnia 10 19.19(4.20-87.60) 19.18 28.72 Urine albumin/creatinine ratio increased 10 19.19(4.20-87.60) 19.18 28.72 Wound 10 19.19(4.20-87.60) 19.18 28.72 Abdominal discomfort 213 18.02(13.10-24.80) 17.76 600.70 Therapy cessation 57 16.88(9.24-30.85) 16.82 157.66 Migraine 74 16.78(9.90-28.44) 16.70 204.28 Peripheral swelling* 136 15.95(10.90-23.35) 15.81 369.30 Blood Pressure Increased 195 15.47(11.30-21.17) 15.26 523.92 Neck pain 15 14.40(4.78-43.39) 14.38 39.34 Dyspepsia 87 13.99(8.90-21.99) 13.90 225.66 Glomerular filtration rate abnormal 14 13.44(4.42-40.83) 13.43 35.79 Chromaturia 10 12.79(3.52-46.50) 12.79 25.08 Ear infection 10 12.79(3.52-46.50) 12.79 25.08 Laboratory test abnormal 88 12.58(8.17-19.36) 12.50 219.00 Muscle spasms 69 12.09(7.48-19.54) 12.03 168.93 Abdominal pain upper 212 11.95(9.10-15.69) 11.79 515.97 Proteinuria 250 11.21(8.77-14.31) 11.02 591.12 PT: preferred term; N: number of adverse events; ROR: reporting odds ratio; 95% CI, 95% confidence interval; PRR: proportional reporting ratio; *: the instruction does not mention. Bold indicates statistically significant signals only compared to other calcineurin inhibitors. Table4 Time to onset and Weibull distribution analysis for PT signals of voclosporin from FAERS. Scale parameter, α (95% CI) Shape parameter, β (95% CI) Voclosporin 13,856 58(3-212) 0-1128 145.92(133.72-158.12) 0.73(0.69-0.76) Early failure N: number of adverse events; IQR, interquartile range; Cl, confidence interval; α, scale parameters; β, shape parameters. Figure legends Figure1 Frequency of reporting of SOCs of voclosporin-related adverse events. A, Frequency of reporting from FAERS. B, Frequency of reporting from VigiBase. Figure2 Time to onset distribution of voclosporin-related adverse events from FAERS. Figure3 DME list screening results for voclosporin from FAERS. Supplementary Material File (figure2.tif) Download 6.10 MB File (figure3.tif) Download 6.38 MB Information & Authors Information Version history V1 Version 1 29 July 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations Jingjing Wang Zhengzhou University College of Public Health View all articles by this author Yongli Yang Zhengzhou University College of Public Health View all articles by this author xiaobo chen Henan Food and Drug Administration View all articles by this author Yi Zhang Zhengzhou University College of Public Health View all articles by this author Xue Yang Henan Food and Drug Administration View all articles by this author Ying Qiao Zhengzhou University College of Public Health View all articles by this author Xudong Xia 0009-0008-0543-4947 Zhengzhou University College of Public Health View all articles by this author Xiaocan Jia 0000-0003-0895-2957 [email protected] Zhengzhou University College of Public Health View all articles by this author Metrics & Citations Metrics Article Usage 181 views 130 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Jingjing Wang, Yongli Yang, xiaobo chen, et al. Real-world pharmacovigilance study of voclosporin based on FAERS and VigiBase. Authorea . 29 July 2025. DOI: https://doi.org/10.22541/au.175381768.85031512/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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