Postmarketing safety evaluation of belimumab: a pharmacovigilance analysis

Abstract

Objective

The present study aimed to provide a comprehensive evaluation of the postmarketing safety of belimumab based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Methods

Adverse event (AE) reports in the FAERS database from January 2021 to December 2023 were extracted to perform the disproportionality analysis by calculating the reporting OR. The clinical characteristics and onset times of AEs were investigated. The differences across ages and regions in belimumab-related AEs were also explored.

Results

A total of 4 974 201 AE reports were retrieved from the FAERS database, among which 9782 reports were related to belimumab. 485 positive safety signals related to belimumab were identified. In addition to the labelled AEs, such as depression and infections, new unexpected AEs, including product dose omission issue and inappropriate schedule of product administration, were identified. The median onset time of belimumab-related AEs was 75 days. Moreover, our analysis revealed frequently reported AEs in paediatric patients, such as systemic lupus erythematosus, and in adult patients, such as injection site pain. Additionally, AEs such as drug ineffective were commonly reported in patients of North America, Asia and Europe, while AEs, including an inappropriate schedule of product administration, had a high incidence in patients of South America.

Conclusion

The current study provides a valuable evaluation of the postmarketing safety of belimumab. Further studies are required to validate and confirm these findings. Clinicians should be vigilant regarding these potential AEs and pay more attention to the proper dosage regimen of belimumab in clinical practice.

WHAT IS ALREADY KNOWN ON THIS TOPIC

• While belimumab shows promising efficacy for the treatment of SLE and lupus nephritis (LN), concerns over its safety profile persist.

• Age and race differences in disease activity and treatment response in SLE have been reported.

WHAT THIS STUDY ADDS

• New unexpected adverse events (AEs) related to belimumab as well as labelled AEs were identified.

• The median onset time of belimumab-related AEs was 75 days.

• Age and region differences in belimumab-related AEs were observed.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• The results suggest the need for a prospective study to validate and confirm the relationships between belimumab and AEs.

• These findings provide valuable vigilance evidence for early detection and appropriate management of belimumab-related AEs in SLE and LN patients.

Introduction

SLE is a complex autoimmune disease that causes severe damage to many organs and tissues and is associated with significant morbidity and mortality due to delayed diagnosis, renal involvement and major cardiovascular events.¹,³ The prevalence of SLE varies from 50 to 100 cases per 100 000 individuals per year and has surged due to improved diagnostic techniques and international data availability.^{4 5} SLE has complex clinical heterogeneity in diverse patient populations. It has been reported that paediatric patients with childhood-onset SLE are more likely to have severe disease activity, systemic manifestations and faster damage accrual over time compared with patients with SLE starting in adulthood.^{6 7} In addition, there might be a potential genetic predisposition to SLE as Asian populations had a higher prevalence of SLE and an increased risk of frequent and severe clinical manifestations and mortality compared with Caucasian populations.⁸,¹⁰ Moreover, patients of African ancestry and Latin Americans generally had worse disease severity.¹¹

Belimumab is the first human monoclonal antibody that was approved by the Food and Drug Administration for the treatment of paediatric and adult patients with active SLE.¹² It has been reported that B lymphocyte stimulator (BLyS) was overexpressed in patients with SLE and correlated with the disease activity.¹³ By targeting the BLyS and thus inhibiting B cell activation and maturation, belimumab significantly ameliorated disease activity, reduced the daily glucocorticoid doses and flare incidence and prevented the damage progression in patients with SLE.¹⁴,¹⁶ Lupus nephritis (LN) is a cardinal manifestation of the SLE that affects 30–40% of SLE patients and contributes significantly to increased medical expenses, disease progression and mortality in SLE patients.¹⁷,¹⁹ Based on the promising results in a multinational clinical trial, belimumab recently received its approval for the treatment of adult patients with active LN in the USA and the European Union.²⁰

With the widespread use of belimumab in clinics, adverse events (AEs), such as serious infections, pneumonia and psychiatric disorders, have been frequently reported in previous studies.^{13 21} Discontinuation of belimumab treatment due to AEs, including lack of effectiveness, hyperthyroidism and pulmonary tuberculosis, was also observed in SLE and LN patients.^{13 22 23} Moreover, AEs of special interest, such as malignancies, depression and suicides, had raised great concerns during the treatment of belimumab in the clinic.^{24 25} However, these studies are generally limited by the small sample sizes, the strict inclusion and exclusion criteria, or short follow-up periods. The postmarketing safety profile of belimumab remains insufficiently explored. In the present study, we aimed to comprehensively evaluate the postmarketing safety of belimumab to provide valuable information for the safe and rational use of belimumab in clinics based on the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database.

Materials and methods

Data source

FAERS is a publicly accessible database that collects AE reports submitted by healthcare professionals, patients and pharmaceutical companies all over the world to support postmarketing drug safety surveillance. In this study, AE reports from 2021 to 2023 were extracted from the FAERS database. The detailed information related to AEs was covered across seven datasets in the FAERS database: DEMO (demographic characteristics), DRUG (drug regimen), REAC (adverse events), INDICATION (dosing indications), OUTC (outcomes), THER (start and end date of drug therapy) and RSPR (reporting sources). Before analysis, we followed the FDA recommendations and removed the duplicated reports based on the PRIMARYID and CASEID in the DEMO file: choose the most recent FDA_DT (report date) when the CASEID (case ID) was the same; choose the higher PRIMARYID (report ID) when the CASEID and FDA_DT were the same. Both the brand name (belimumab) and generic name (benlysta) approved by the FDA were employed to acquire the relevant AE reports. Only AE reports that belimumab was classified as the primary suspect role in the DRUG file were included in our analysis to improve accuracy and validity. AEs in FAERS were coded by preferred terms (PTs) and categorised into system organ classes (SOCs) from the Medical Dictionary for Regulatory Activities.

Data mining

Clinical characteristics such as gender, age, reporting country, indications and outcomes were collected to provide a comprehensive description of AE reports. Time to onset was calculated as the time interval between the date of belimumab initiation (START_DT in the THER dataset) and the date of AE occurrence (EVENT_DT in the DEMO dataset). AEs with incomplete or inaccurate date entries were excluded.

Disproportionality analysis was commonly used in pharmacovigilance studies to identify drug-related AE signals that are more frequently reported than expected by estimating the proportion of specific drug AE within the full database. In the present study, disproportionality analysis was conducted to evaluate the possible relationship between belimumab and AEs by calculating the reporting OR (ROR) (online supplemental table 1). A higher ROR value indicates a stronger association between belimumab and the AE. Data processing and analysis were performed using SQL, Microsoft Excel, SPSS V.23.0 and GraphPad Prism 8.

Patient and public involvement

Patients and/or public were not involved in the study design or dissemination of this pooled analysis.

Results

Clinical characteristics of AE reports

In the present study, a total of 4 974 201 AE reports were extracted, and 9782 AE reports were identified to be related to belimumab. The clinical characteristics of belimumab-related AE reports are documented in table 1. Female subjects (60.72%) accounted for an overwhelming proportion of the AE reports, which was consistent with the striking female predominance of SLE. Patients aged 18–65 years (24.00%) tended to have a higher incidence of belimumab-related AEs. Of note, patients younger than 18 years (1.07%) also accounted for a small proportion of the total reports. The majority of reports were submitted by the USA (71.43%), followed by Japan (6.14%) and Brazil (4.76%). The most common outcome was other medical events, accounting for 28.70% of the total reports, followed by hospitalisation and death, which accounted for 9.55% and 1.63% of the total reports, respectively. The most frequently reported indications for belimumab were systemic lupus erythematosus and lupus nephritis, which were consistent with the approved indications by the FDA. The numbers of AE reports were relatively constant from 2021 to 2023.

Table 1. Clinical characteristics of AEs related to belimumab from the FAERS database.

Characteristics	Cases (n)	Proportion (%)
	9782
Sex
Female	5940	60.72
Male	426	4.35
Unknown	3416	34.92
Age (years)
<18	105	1.07
18≤ and＜64	2348	24.00
≥65	407	4.16
Unknown	6922	70.76
Indications (top five)
Product used for unknown indication	4329	44.25
Systemic lupus erythematosus	4208	43.02
Lupus nephritis	199	2.03
Prophylaxis	91	0.93
COVID-19 prophylaxis	30	0.31
Serious outcome
Other important medical events	2807	28.70
Hospitalization-initial or prolonged	934	9.55
Death	159	1.63
Life-threatening	29	0.30
Disabled	8	0.08
Required intervention	5	0.05
Congenital anomaly	2	0.02
Reported countries (top five)
USA	6987	71.43
Japan	601	6.14
Brazil	466	4.76
Canada	329	3.36
Argentina	88	0.90
Reporting year
2023	3616	36.97
2022	3511	35.89
2021	2655	27.14

AE, adverse event; FAERS, Food and Drug Administration Adverse Event Reporting System

Signal mining

In the present study, belimumab-related positive signals were identified across 27 SOCs based on the disproportionality analysis. The proportion of positive signals related to belimumab at the SOC level is shown in figure 1. The most frequently reported SOCs were injury, poisoning and procedural complications (SOC: 10022117), general disorders and administration site conditions (SOC: 10018065) and infections and infestations (SOC: 10051905). A total of 485 PT signals were identified in the current study (table 2). AEs including depression, fever and infection were detected, which were in line with the drug label. Notably, new unexpected AEs uncovered on the label of belimumab were also identified, such as arthralgia, product dose omission issue and condition aggravated. Moreover, the most frequently reported PTs were product dose omission issue (n=2914, ROR=11.52), and lupus enteritis has the strongest signal value intensity (n=11, ROR=931.47). Additionally, although some PTs, including lupus pancreatitis (n=4, ROR=253.86), masticatory pain (n=6, ROR=169.27) and neuropsychiatric lupus (n=8, ROR=123.13), had high signal value intensity, they were reported with a small number of cases, which deserved more attention and further research.

Figure 1. Proportion of positive signal for belimumab-related adverse events at the system organ class level.

Table 2. Sensitivity analysis of belimumab-related AEs at the PT level in FAERS database (n>100).

SOC	PT	Cases (n)	Reporting OR (95% CI)
General disorders and administration site conditions
	Pain	709	1.56 (1.44 to 1.68)
	Fatigue	650	1.35 (1.24 to 1.46)
	Injection site pain	623	4.63 (4.27 to 5.03)
	Malaise	519	2.47 (2.26 to 2.69)
	Fever	461	2.41 (2.19 to 2.64)
	Condition aggravated	417	1.78 (1.61 to 1.96)
	Asthenia	248	1.29 (1.13 to 1.46)
	Illness	229	1.78 (1.56 to 2.03)
	Injection site haemorrhage	209	5.05 (4.40 to 5.79)
	Feeling abnormal	165	1.37 (1.18 to 1.60)
	Injection site bruising	159	4.82 (4.12 to 5.65)
	Chest pain	155	2.04 (1.74 to 2.39)
	Swelling	150	2.46 (2.09 to 2.89)
	Peripheral swelling	145	1.28 (1.09 to 1.51)
	Inflammation	119	3.12 (2.60 to 3.74)
	Chills	114	1.68 (1.40 to 2.02)
	Ill-defined disorder	107	1.85 (1.53 to 2.24)
Immune system disorders
	Hypersensitivity	143	1.49 (1.26 to 1.75)
Infections and infestations
	COVID-19	467	1.50 (1.37 to 1.65)
	Influenza	362	6.08 (5.47 to 6.76)
	Urinary tract infection	302	2.92 (2.60 to 3.28)
	Pneumonia	217	1.30 (1.14 to 1.49)
	Nasopharyngitis	191	1.61 (1.39 to 1.85)
	Sinusitis	151	2.18 (1.86 to 2.56)
	Infection	133	1.53 (1.29 to 1.82)
Injury, poisoning and procedural complications
	Product dose omission issue	2914	11.52 (11.03 to 12.04)
	Inappropriate schedule of product administration	824	4.47 (4.16 to 4.80)
	Wrong technique in device usage process	623	18.18 (16.74 to 19.75)
	Circumstance or information capable of leading to medication error	405	18.74 (16.93 to 20.73)
	Accidental exposure to product	396	6.37 (5.76 to 7.05)
	Exposure via skin contact	371	64.47 (57.77 to 71.94)
	Underdose	350	11.46 (10.29 to 12.77)
Injury, poisoning and procedural complications
	Product storage error	305	4.52 (4.03 to 5.07)
	Incorrect dose administered	232	1.66 (1.46 to 1.90)
	Exposure during pregnancy	181	5.10 (4.40 to 5.92)
	Device use error	115	8.29 (6.88 to 9.97)
Investigations
	Weight decreased	291	1.68 (1.50 to 1.89)
	Weight increased	255	1.89 (1.67 to 2.14)
Musculoskeletal and connective tissue disorders
	Systemic lupus erythematosus	849	34.08 (31.70 to 36.63)
	Arthralgia	544	1.93 (1.77 to 2.10)
	Pain in extremity	291	1.81 (1.61 to 2.03)
	Back pain	164	1.26 (1.08 to 1.47)
	Myalgia	123	1.65 (1.38 to 1.97)
Nervous system disorders
	Headache	557	1.75 (1.60 to 1.90)
	Migraine	110	2.01 (1.66 to 2.42)
Product issues
	Product complaint	570	28.12 (25.78 to 30.66)
	Product availability issue	319	12.58 (11.24 to 14.08)
Psychiatric disorders
	Depression	196	2.05 (1.78 to 2.36)
	Insomnia	153	1.24 (1.06 to 1.46)
Renal and urinary disorders
	Lupus nephritis	117	123.64 (100.95 to 151.45)
Respiratory, thoracic and mediastinal disorders
	Cough	334	1.87 (1.68 to 2.09)
	Oropharyngeal pain	214	3.50 (3.06 to 4.01)
	Rhinorrhoea	134	3.10 (2.61 to 3.68)
Skin and subcutaneous tissue disorders
	Alopecia	157	1.51 (1.29 to 1.77)
	Erythema	138	1.45 (1.23 to 1.72)
Social circumstances
	Social problem	201	182.38 (155.10 to 214.45)
Surgical and medical procedures
	Therapy interrupted	284	4.07 (3.62 to 4.59)
	Hospitalisation	209	2.34 (2.04 to 2.68)
	Surgery	117	3.90 (3.25 to 4.69)

AE, adverse event; FAERS, Food and Drug Administration adverse event reporting systemPTpreferred termSOCsystem organ class

Time to onset of belimumab-related AEs

A total of 1443 AE cases were reported with available onset times. The median onset time was 75 days (IQR 1–554 days). The majority of belimumab-related AEs occurred within the first month (43.24%) after belimumab initiation (figure 2). Of note, a considerable proportion (31.81%) of AEs occurred 1 year or more after the treatment of belimumab.

Figure 2. Onset time of belimumab-related adverse events. d, days.

Subgroup analysis

The results of the disproportionality analysis stratified by patient age are illustrated in figure 3. ‘Product dose omission issue’ was reported with the highest number of cases in all patients. In patients aged<18, ‘systemic lupus erythematosus’ was frequently reported. Interestingly, ‘condition aggravated’ and ‘drug ineffective’ were also present among the top 15 frequently reported AEs. Of note, they were uncommon in patients aged 18–64 and >64. On the other hand, AEs, including ‘wrong technique in device usage process’, ‘product complaint’ and ‘accidental exposure to product’ that were common in patients aged <18, were also frequently reported in patients aged 18–64 and >64. However, AEs that were frequently reported in patients aged 18–64 and >64, such as ‘injection site pain’, ‘pain’ and ‘fatigue’ were rarely reported in patients aged <18.

Figure 3. The top 15 frequently reported belimumab-related adverse events in patients aged younger than 18 (A), aged 18–64 (B) and aged older than 64 (C).

We further investigated the differences in belimumab-related AEs across different regions. Based on the top 10 reporter countries that submitted 89.59% of the total reports, we defined four regions: North America (USA and Canada), South America (Brazil, Argentina and Columbia), Asia (Japan and China) and Europe (France, German and Spain). Figure 4 shows the finding stratified by reporter region. Significant differences were observed in the top 15 frequently reported AEs among different regions. However, systemic lupus erythematosus was frequently reported in all regions. It is noteworthy that drug ineffective was present in the top 15 frequently reported AEs in three regions (North America, Asia and Europe) except for South America. Interestingly, condition aggravated was also observed in the top 15 frequently reported AEs in Asia and Europe.

Figure 4. The top 15 frequently reported belimumab-related adverse events in patients of North America (A), South America (B), Asia (C) and Europe (D).

Discussion

In the current study, we conducted a postmarketing pharmacovigilance analysis of belimumab based on the FAERS database. In addition to the labelled AEs, we identified new unexpected AEs related to belimumab. We further investigated the onset time and the potential age and region differences of the identified AEs. These findings may provide new evidence for the update of drug label and the rational and safer use of belimumab in clinical practice.

In the present study, the most frequently reported AEs by SOC were ‘injury, poisoning and procedural complications’, ‘general disorders and administration site conditions’, ‘infections and infestations’ and ‘musculoskeletal and connective tissue disorders’. Consistently, infections and infestations and musculoskeletal and connective tissue disorders by SOC were frequently reported to be related to belimumab in previous studies.²¹²⁴,²⁶ At the ‘injury, poisoning and procedural complications’ level, the most frequently reported AEs by PT were ‘product dose omission issue’, ‘wrong technique in device usage process’ and ‘inappropriate schedule of product administration’. Other procedural complications, such as ‘incorrect dose administered’ and ‘product storage error’, were commonly reported as well. Interestingly, ‘product issues’ by SOC and the AEs by PT at this level, including ‘product complaint’ and ‘product availability issue’, were also identified to be positive safety signals related to belimumab. With the increasing use of belimumab, there were likely more errors related to the administration of belimumab. Potentially inappropriate medications could significantly enhance serious adverse drug reactions and increase the likelihood of hospitalisations.²⁷ Therefore, as belimumab has a systemic dosage regimen, preparation instructions and administration instructions according to the drug label, close attention should be paid to the correct disposition and proper dosage regimen of belimumab in clinical practice. At the ‘general disorders and administration site conditions’ level, the commonly reported AEs by PT included ‘fever’, ‘pain’ and ‘injection site reactions’, which was in line with the drug label. At the ‘musculoskeletal and connective tissue disorders’ level, the most frequently reported AE by PT was systemic lupus erythematosus, which was the indication for belimumab. Since FAERS collects all medical and health-related PTs, it will also contain some non-drug-related AE signals that may be caused by disease progression or other causes. Therefore, the recorded systemic lupus erythematosus might indicate flaring of the disease or lack of response rather than a side effect of belimumab.²⁵

In the present study, depression and suicidal ideation were identified as positive safety signals related to belimumab, which was consistent with the drug label. Previous studies have frequently reported an increased risk of psychiatric and neurological AEs, such as depression in belimumab-treated SLE patients.^{23 28 29} Suicide and self-injury related to belimumab were also reported in the treatment of patients with SLE and LN.^{23 30 31} However, in a meta-analysis, belimumab was found to be neutrally related to the risk of depression and did not show an increased risk of suicidal or self-injury behaviours.²¹ Moreover, belimumab-related depression, suicides and self-injury were not observed in several studies.^{6 10 32} Interestingly, belimumab was effective and safe to treat the neuropsychiatric manifestations of SLE in some cases.³³ It should be noted that neuropsychiatric events, such as seizures and cognitive dysfunction, were diverse and frequent around SLE diagnosis.^{34 35} Depression and anxiety also had a high prevalence in childhood-onset SLE (cSLE).^{36 37} Of note, it has been reported that belimumab-related psychiatric disorders had a higher risk in patients with a preceding history of psychiatric diseases.³⁸ Therefore, whether the psychiatric disorders are related to belimumab or the diseases requires further research. More attention should be paid to patients with a history of depression and suicidal ideation before initiating belimumab treatment.

Consistent with the drug label, positive safety signals of infections, including influenza, urinary tract infection and progressive multifocal leucoencephalopathy were identified in the current study. Infections related to belimumab, such as nasopharyngitis and viral upper respiratory tract infection, were frequently reported in paediatric and adult patients with SLE.^{10 13 39} Belimumab-related infections were also commonly reported in LN patients.²² As belimumab acted to decrease B cell number and inhibit B cell function, the increased risk of infections might be due to the immunomodulatory activity of belimumab.⁴⁰ However, it has been reported that patients with SLE might have ‘a variable net state of immunosuppression’.¹¹ Therefore, SLE patients had an intrinsically increased risk of infections that could be expanded by immunosuppressive therapy.⁴¹ The frequently reported infections might be due to the concomitant steroids and immunosuppressants rather than belimumab.²² Interestingly, by targeting T cells and their subsets via interleukin-6, belimumab combined with low-dose cyclophosphamide significantly reduced the risk of infections compared with the standard dose in SLE patients.⁴¹ In addition, add-on treatment with belimumab reduced the risk of serious AEs such as respiratory tract infection in LN patients, which might be related to the steroid-sparing effect of belimumab.^{18 42} Due to the high heterogeneity of these findings, further studies are required to elucidate the relationship between belimumab and infections. Nevertheless, close monitoring and prompt treatment for any infections are essential for patients with SLE. In addition, vaccination against infections such as seasonal influenza and pneumococcal infections is highly recommended.

Among AEs with available age information, patients aged 18 years and older accounted for 96.31% of the total AE reports, indicating that adult patients might be the major users of belimumab. Of note, a small proportion of AE reports were from paediatric patients. Though the incidence of cSLE was relatively low, more attention should be paid to these patients, as patients with cSLE had a higher disease activity and faster damage accrual over time and a worse prognosis compared with those with adulthood-onset.^{6 43 44} Consistently, in the subgroup analysis stratified by age, ‘drug ineffective’ and ‘condition aggravated’ were observed among the top 15 frequently reported AEs only in patients aged <18. Moreover, the frequently reported ‘systemic lupus erythematosus’ might be disease-related rather than treatment-related. It is noteworthy that AEs such as ‘product dose omission issue’, ‘inappropriate schedule of product administration’ and ‘wrong technique in device usage process’ were frequently reported in both paediatric and adult patients with SLE, which highlighted the importance of proper dosage regimen.

The prevalence and severity of SLE varied across different racial backgrounds. Therefore, we further explored the potential racial difference in belimumab-related AEs. There were significant differences among the top 15 frequently reported AEs across different regions. ‘Systemic lupus erythematosus’ was frequently reported in all four regions, possibly due to the high incidence of flares or lack of responses.^{5 25} Indeed, our analysis observed that ‘drug ineffective’ and ‘condition aggravated’ were commonly reported in patients of Asia and Europe. Moreover, ‘drug ineffective’ also had a high frequency in patients of North America. However, neither ‘drug ineffective’ nor ‘condition aggravated’ were observed among the top 15 frequently reported AEs in patients of South America. It has been reported that 40% of SLE patients did not show a clinically meaningful response to belimumab in clinical trials.⁴⁵ Lack of response seemed to be the common reason for belimumab discontinuation.³⁸ In a multicentre observational study, 9.38% of patients discontinued the treatment of belimumab due to lack of effectiveness.¹³ However, as AEs such as product dose omission issue and inappropriate schedule of product administration were frequently reported, the underlying reasons for drug ineffective and condition aggravated related to belimumab require further investigation.

Most AEs occurred within the first month after belimumab initiation, which emphasised the importance of early detection and close monitoring during the initial treatment phase. However, a considerable proportion of AE cases might still occur after 1 year of belimumab treatment. It has been reported that the annual incidence of all AEs remained stable or declined over time.^{23 24} However, AEs such as upper respiratory tract infections, cough and nasopharyngitis increased through study years 2–3 before stabilising or decreasing from thereon.²³ Moreover, belimumab-related deaths were occasionally reported in the long-term extension trials.^{46 47} Therefore, further evaluation of the long-term safety of belimumab remains necessary.

The present study has several limitations. First, FAERS is a spontaneous reporting system that collects AE reports all over the world from healthcare professionals, drug manufacturers and patients. There are inevitably incomplete or inaccurate information due to various factors, such as worldwide differences in reporting and interpretation of AEs, which might contribute to bias of analysis results. For example, the high prevalence of unavailable data for age might introduce bias into the differences between children and adults in the present study. Second, a causal relationship between belimumab and AEs could not be established as the disproportionality analysis only provided a statistical association between belimumab and the detected AEs. Third, as more detailed information and characteristics regarding AE reports such as the prior disease and medication history and drug-drug interactions are lacking, our findings may not be fully representative of clinical practice. Therefore, considering the complex characteristics of SLE and the common combination therapy in clinic, our results should be considered as a valuable reference for clinicians and pharmacists. However, our study for the first time provides a comprehensive evaluation of the postmarketing safety profile of belimumab based on the FAERS database. The differences across ages and regions in belimumab-related AEs were also preliminarily investigated.

In conclusion, the present study performed a comprehensive evaluation of reported AEs related to belimumab, including the onset times and potential age and region differences based on the FAERS database. These findings provide valuable information for improving therapeutic efficacy and AE management in clinical practice. Further prospective studies are required to confirm and validate the associations between belimumab and the detected AEs.

Data availability statement

Data are available upon reasonable request.