Adverse Event Profiles of Monoclonal Antibodies: A Descriptive Analysis of FAERS Data

Abstract

Introduction

Monoclonal antibodies (mAbs) are bioengineered molecules designed to replicate the immune system’s precise targeting of pathogens and abnormal cells. While monoclonal antibodies (mAbs) are targeted therapies, they carry risks like immunogenic reactions and drug interactions.

Objective

The current study utilizes FAERS to describe the distribution of reported adverse events, patient demographics, and reporting patterns associated with selected monoclonal antibody therapies.

Methods

The analysis included all monoclonal antibody adverse event reports in FAERS through March 31, 2025, with subsequent reports and non-monoclonal antibody drugs excluded, and utilized descriptive statistics to present results as numbers and percentages.

Results

FAERS data through March 31, 2025, for 18 monoclonal antibodies showed distinct adverse event (AE) patterns. Most AEs occurred in adults aged 18–64, with females reporting more events except for cancer-related mAbs such as cetuximab (67.09% males) and ipilimumab (64.15% males). Healthcare professionals were the primary reporters, though some drugs—like adalimumab (72.13%)—had mainly consumer reports. Common AEs included injection-site pain (7.44%), rash, in addition to reports categorized as “drug ineffective,” a MedDRA preferred term used in FAERS to reflect reporter perception of treatment failure (e.g., 17.96% for secukinumab; 28.14% for tocilizumab).

Conclusion

The most frequently reported events included treatment-ineffectiveness perceptions and administration issues, which warrant further investigation in controlled studies. Some reports included product use issues such as dose omission or incorrect administration. However, due to the spontaneous reporting nature of FAERS, the relationship between adherence-related issues and clinical outcomes cannot be definitively established. The findings of the study describe reporting patterns in FAERS and may serve as a basis for future pharmacovigilance or epidemiologic research.

Introduction

Monoclonal antibodies (mAbs) are bioengineered molecules designed to replicate the immune system’s precise targeting of pathogens and abnormal cells. ¹ Initially produced through hybridoma cell cultures, modern monoclonal antibodies (mAbs) are now manufactured using recombinant DNA technology in mammalian expression systems. Their antigen specificity derives from the variable domains of the heavy and light chains, particularly the complementarity-determining regions, which enable exact target binding. ² This molecular precision allows mAbs to selectively identify and neutralize specific antigens, making them powerful therapeutic agents. ³ The development of mAbs has transformed modern medicine, providing targeted treatments for diverse conditions, including malignancies, autoimmune diseases, and infections. ⁴ Their exceptional specificity and adaptability have established mAbs as both essential diagnostic tools and highly effective therapies, offering clinicians sophisticated solutions for complex medical challenges. ⁴

Successful treatment with monoclonal antibodies (mAbs) requires careful consideration of their adverse effects and potential drug interactions. ⁵ While mAbs offer targeted therapy, they carry risks of immunogenic reactions, including acute anaphylaxis, serum sickness, and anti-drug antibody formation. Additionally, target-specific adverse effects may occur depending on the mAb’s mechanism of action, ranging from increased infection risk and malignancy to autoimmune phenomena and organ toxicities such as cardiotoxicity. ⁶ According to the American Cancer Society, mAbs are typically administered intravenously and may trigger infusion reactions resembling allergic responses, particularly during initial treatment. Common symptoms include fever, chills, weakness, headache, gastrointestinal disturbances (nausea/vomiting/diarrhea), hypotension, and skin rashes. ⁷ While naked mAbs generally demonstrate better safety profiles than traditional chemotherapy agents, they can still produce significant adverse effects in certain patients. ⁷

Adverse drug events (ADEs) - unintended harmful medication effects - significantly contribute to preventable hospital admissions and deaths. Effective pharmacovigilance systems rely on thorough ADE detection and reporting to monitor drug safety across their entire lifespan. ⁸ These systems are particularly vital for uncovering rare severe reactions, long-term complications, and clinically important interactions that pre-approval trials often miss due to limited sample sizes and durations. ⁸ However, persistent underreporting of ADEs, even where mandatory, creates surveillance gaps that may delay identification of critical safety issues, potentially endangering patients. ⁸

The FDA Adverse Event Reporting System (FAERS) plays a pivotal role in post-marketing drug safety surveillance, providing essential data that informs regulatory decisions such as drug labeling changes and safety alerts.^9,10 This comprehensive database contains more than 28 million reports submitted by healthcare providers, patients, and manufacturers, serving as a vital tool for pharmacovigilance research. Improved reporting mechanisms and standardized data formats have substantially enhanced FAERS’ utility and reporting efficiency.^9,11

Several pharmacovigilance studies utilizing the FAERS database have primarily focused on either individual monoclonal antibodies or specific categories of adverse events. For instance, Tang et al conducted a disproportionality analysis examining adverse events associated with ixekizumab, providing detailed insights into the safety profile of a single agent. ¹² Similarly, Zhou et al investigated thromboembolic events linked to antiangiogenic monoclonal antibodies, focusing on a specific adverse event across a defined drug class. ¹³ While such studies offer valuable drug-specific or event-specific safety signals, they do not provide a broader comparative perspective across multiple monoclonal antibodies with diverse mechanisms of action and clinical indications. Therefore, the current study utilizes FAERS to describe the distribution of reported adverse events, patient demographics, and reporting patterns associated with selected monoclonal antibody therapies. By providing a comprehensive and up-to-date pharmacovigilance overview across multiple agents, the study seeks to identify clinically relevant safety signals and inform strategies to enhance patient adherence, optimize monitoring practices, and improve patient education in real-world settings.

Methods

Data Source and Collection

This descriptive retrospective study utilized the FDA Adverse Event Reporting System (FAERS) to evaluate pharmacovigilance patterns associated with monoclonal antibodies (mAbs). Data were extracted using the publicly available FAERS Public Dashboard, covering reports submitted from Q1 2004 through Q1 2025. FAERS is a key post-marketing surveillance system that supports regulatory decision-making, including safety communications and drug labeling updates. Adverse events were coded using the Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms (PTs) as recorded in the FAERS database. Frequently reported events were summarized at the PT level. The terms “ineffective drug” and “product use issues” were used as defined within FAERS and reflect reporter-submitted MedDRA PTs. These terms do not necessarily indicate confirmed therapeutic failure or nonadherence but rather represent the reporter’s perception of reduced or absent therapeutic effect.

Drug Selection

A total of 18 monoclonal antibodies were included in the analysis. These agents were selected based on a combination of criteria, including their frequency of reporting in the FAERS database, therapeutic diversity across multiple clinical indications (e.g., oncology, autoimmune diseases, and infectious diseases), and their widespread clinical use during the study period. This selection approach was intended to ensure representativeness of commonly used mAbs while capturing variability in safety reporting across different therapeutic classes.

Inclusion and Exclusion Criteria

The study included all adverse event reports associated with the selected monoclonal antibodies submitted to FAERS up to March 31, 2025. Reports submitted after this date or involving medications other than the selected monoclonal antibodies were excluded.

Data Collection

Extracted variables included patient demographics (age and sex), reporter type (healthcare professionals vs. non-healthcare professionals), and the most frequently reported adverse events for each monoclonal antibody.

Data Processing

FAERS data contain inherent limitations, including duplicate reports, incomplete demographic data, and reporting bias. Duplicate case reports were managed according to FDA recommendations using the CASEID and PRIMARYID structure. When multiple records corresponded to the same CASEID, only the most recent version of the report was retained for analysis. Although the FAERS Public Dashboard provides pre-processed data with partial deduplication, additional review was conducted where possible to minimize duplicate inclusion. Based on prior FAERS-based studies and FDA documentation, duplicate reports are estimated to account for approximately 8–12% of total records. This range is consistent with the expected level of duplication in spontaneous reporting systems and was considered during data interpretation. The reporter country field was reviewed when available to assess potential cross-regional duplicate reporting. Reports with missing demographic variables were retained and categorized as “unknown” where appropriate to preserve dataset completeness.

Data Analysis

Data were analyzed using descriptive statistics, and results were reported as absolute counts and percentages. This study was designed as a descriptive pharmacovigilance analysis aimed at characterizing reporting patterns rather than detecting statistical safety signals. Therefore, disproportionality analyses, including reporting odds ratios (ROR), proportional reporting ratios (PRR), information components (IC), and empirical Bayes geometric means (EBGM), were not performed.

Ethical Approval

This study utilized publicly available, de-identified data from the FDA Adverse Event Reporting System (FAERS). Since the data did not include patient identifiers and were obtained from an open-access federal database, the research did not qualify as human subjects research under U.S. regulations (45 CFR 46) and therefore did not require approval from an Institutional Review Board (IRB).

Results

The Included Monoclonal Antibodies

Eighteen monoclonal antibodies, used for treating various conditions, were included in the study (Table 1).

Table 1.

Monoclonal Antibodies, Their Therapeutic Targets, and Clinical Applications

Monoclonal antibody	Target	Primary uses
Adalimumab	TNF-α	Rheumatoid arthritis, psoriasis, Crohn’s disease, ulcerative colitis
Alemtuzumab	CD52	Chronic lymphocytic leukemia, multiple sclerosis
Bevacizumab	VEGF	Colorectal, lung, ovarian cancer, macular degeneration
Cetuximab	EGFR	Colorectal cancer, head & neck cancer
Daratumumab	CD38	Multiple myeloma
Dupilumab	IL-4/IL-13 receptor	Atopic dermatitis, asthma, nasal polyps
Eculizumab	Complement protein C5	Paroxysmal nocturnal hemoglobinuria, aHUS
Infliximab	TNF-α	Crohn’s disease, ulcerative colitis, rheumatoid arthritis
Ipilimumab	CTLA-4	Melanoma
Nivolumab	PD-1	Melanoma, lung cancer, renal cell carcinoma
Omalizumab	IgE	Severe allergic asthma, chronic idiopathic urticaria
Palivizumab	RSV F protein	Prevention of RSV in high-risk infants
Pembrolizumab	PD-1	Melanoma, lung cancer, Hodgkin’s lymphoma
Rituximab	CD20 (B cells)	Non-Hodgkin’s lymphoma, CLL, rheumatoid arthritis
Secukinumab	IL-17A	Psoriasis, ankylosing spondylitis
Tocilizumab	IL-6 receptor	Rheumatoid arthritis, cytokine release syndrome (e.g., COVID-19)
Trastuzumab	HER2/neu receptor	HER2-positive breast & gastric cancer
Ustekinumab	IL-12/23 inhibitor	Psoriasis, crohn’s Disease, Ulcerative Colitis

Comparative Patterns of Adverse Events Across Monoclonal Antibodies

Across the 18 monoclonal antibodies analyzed in the FAERS database through March 31, 2025, several consistent demographic and reporting patterns were observed. Most adverse event reports involved adults aged 18–64 years, reflecting the primary population receiving monoclonal antibody therapies for autoimmune diseases and malignancies. Female predominance was noted for several agents commonly used in autoimmune and inflammatory conditions, including adalimumab, dupilumab, secukinumab, tocilizumab, and ustekinumab. In contrast, a higher proportion of male reports was observed for oncology-related therapies such as cetuximab, ipilimumab, nivolumab, and daratumumab, which likely reflects the epidemiology of certain cancers.

Healthcare professionals were responsible for the majority of adverse event reports for most oncology-administered monoclonal antibodies, including bevacizumab, daratumumab, pembrolizumab, nivolumab, and trastuzumab, consistent with their administration in hospital or specialized clinical settings. Conversely, a higher proportion of consumer reports was observed for monoclonal antibodies frequently self-administered in outpatient settings, such as adalimumab and secukinumab.

Across drug classes, several commonly reported adverse event categories emerged. These included gastrointestinal symptoms (e.g., nausea, vomiting, and diarrhea), dermatologic reactions (e.g., rash and pruritus), musculoskeletal complaints (e.g., arthralgia and joint swelling), infections (e.g., pneumonia and upper respiratory infections), and administration-related events such as infusion reactions or injection-site pain. Reports of “ineffective drug,” off-label use, and product-use issues were also frequently documented across multiple monoclonal antibodies. Additionally, serious outcomes such as death and disease progression were frequently reported for several oncology-related monoclonal antibodies; however, these outcomes likely reflect the severity of the underlying malignancies rather than direct drug toxicity. Detailed adverse event distributions for each monoclonal antibody are summarized in Tables 2–19.

Table 3.

The most reported adverse events of alemtuzumab.

Variable	Category	Number of Cases	Percentage
Age	0-1 Month	32	0.26
	2 Months-2 Years	461	3.75
	3-11 Years	639	5.20
	12-17 Years	358	2.92
	18-64 Years	9370	76.32
	65-85 Years	1387	11.30
	More than 85 Years	30	0.24
Gender	Female	8233	58.92
​	Male	5739	41.08
Specialty of the reporters	Healthcare Professional	13245	78.51
​	Consumer	3625	21.49
The most reported adverse events	Headache	1817	10.55
	Fatigue	1797	10.43
	Pyrexia	1778	10.32
	Rash	1234	7.16
	Off-Label Use	1224	7.10
	Nausea	1141	6.62
	Dyspnea	966	5.61
	Asthenia	920	5.34
	Decreased Lymphocyte Count	859	4.99
	Multiple Sclerosis Relapse	815	4.73
	Urinary Tract Infection	757	4.39
	Pain	729	4.23
	Immune Thrombocytopenia	728	4.23
	Ineffective Drug	716	4.16
	Decreased Platelet Count	689	4.00
	Pneumonia	676	3.92
	Cough	661	3.84
	Decreased White Blood Cell Count	655	3.80

Table 4.

The most reported adverse events of bevacizumab.

Variable	Category	Number of Cases	Percentage
Age	0-1 Month	32	0.04
	2 Months-2 Years	146	0.21
	3-11 Years	611	0.88
	12-17 Years	422	0.61
	18-64 Years	36856	52.98
	65-85 Years	30401	43.70
	More than 85 Years	1099	1.58
Gender	Female	45974	53.48
	Male	39992	46.52
Specialty of the reporters	Healthcare Professional	86262	84.90
	Consumer	15337	15.10
The most reported adverse events	Death	11642	11.19
	Off-Label Use	11227	10.79
	Disease Progression	6598	6.34
	Diarrhea	6378	6.13
	Nausea	5566	5.35
	Fatigue	5339	5.13
	Hypertension	5106	4.91
	Vomiting	4342	4.17
	Anemia	3746	3.60
	Pyrexia	3529	3.39
	Neutropenia	3390	3.26
	Asthenia	3077	2.96
	Decreased Appetite	3058	2.94
	Dyspnea	2834	2.72
	Proteinuria	2668	2.56
	Thrombocytopenia	2656	2.55
	Ineffective Drug	2572	2.47
	Abdominal Pain	2567	2.47

Table 5.

The most reported adverse events of cetuximab.

Variable	Category	Number of Cases	Percentage
Age	0-1 Month	3	0.01
	2 Months-2 Years	1	0.00
	3-11 Years	21	0.10
	12-17 Years	24	0.12
	18-64 Years	11178	54.15
	65-85 Years	9218	44.65
	More than 85 Years	198	0.96
Gender	Female	7873	32.91
	Male	16047	67.09
Specialty of the reporters	Healthcare Professional	17817	65.85
	Consumer	9239	34.15
The most reported adverse events	Rash	2229	7.95
	Diarrhea	1841	6.57
	Nausea	1537	5.48
	Off-Label Use	1442	5.14
	Vomiting	1319	4.71
	Dyspnea	1289	4.60
	Neutropenia	1136	4.05
	Dehydration	1127	4.02
	Infusion Related Reaction	1110	3.96
	Pyrexia	1037	3.70
	Fatigue	928	3.31
	Hypotension	904	3.23
	Decreased Appetite	897	3.20
	Anemia	837	2.99
	Dermatitis Acneiform	833	2.97
	Mucosal Inflammation	802	2.86
	Death	794	2.83
	Asthenia	765	2.73

Table 6.

The most reported adverse events of daratumumab

Variable	Category	Number of Cases	Percentage
Age	0-1 Month	2	0.01
	2 Months-2 Years	34	0.19
	3-11 Years	75	0.43
	12-17 Years	63	0.36
	18-64 Years	6671	38.10
	65-85 Years	10260	58.59
	More than 85 Years	406	2.32
Gender	Female	8815	43.39
	Male	11500	56.61
Specialty of the reporters 25384	Healthcare Professional	23399	92.18
	Consumer	1985	7.82
The most reported adverse events	Plasma Cell Myeloma	2820	11.04
	Infusion Related Reaction	2369	9.27
	Off-Label Use	2341	9.16
	Pneumonia	1387	5.43
	Neutropenia	1292	5.06
	Thrombocytopenia	1040	4.07
	Ineffective Drug	1036	4.06
	Death	1031	4.04
	Pyrexia	967	3.79
	Neuropathy Peripheral	929	3.64
	Dyspnea	927	3.63
	Anemia	881	3.45
	Diarrhea	879	3.44
	Fatigue	764	2.99
	Intentional Product Use Issue	664	2.60
	Covid-19	651	2.55
	Disease Progression	631	2.47
	Nausea	609	2.38

Table 7.

The most reported adverse events of dupilumab.

Variable	Category	Number of Cases	Percentage
Age	0-1 Month	26	0.01
	2 Months-2 Years	2694	1.26
	3-11 Years	15124	7.07
	12-17 Years	16360	7.65
	18-64 Years	138283	64.65
	65-85 Years	38538	18.02
	More than 85 Years	2863	1.34
Gender 299145	Female	182931	61.15
	Male	116214	38.85
Specialty of the reporters 320119	Healthcare Professional	252988	79.03
	Consumer	67131	20.97
The most reported adverse events	Pruritus	36342	11.35
	Product Use in Unapproved Indication	28428	8.88
	Dermatitis Atopic	27005	8.43
	Rash	26345	8.23
	Injection Site Pain	22269	6.95
	Ineffective Drug	20336	6.35
	Dose Omission Issue	19501	6.09
	Dry Skin	17476	5.46
	Eczema	16610	5.19
	Condition Aggravated	13135	4.10
	Arthralgia	12697	3.96
	Inappropriate Schedule of Product Administration	12097	3.78
	Product Use Issue	10501	3.28
	Skin Exfoliation	10137	3.16
	Asthma	9794	3.06
	Dry Eye	9361	2.92
	Erythema	9043	2.82
	Off-Label Use	8501	2.65

Table 8.

The most reported adverse events of eculizumab.

Variable	Category	Number of Cases	Percentage
Age	0-1 Month	88	0.57
	2 Months-2 Years	497	3.20
	3-11 Years	829	5.35
	12-17 Years	639	4.12
	18-64 Years	10003	64.50
	65-85 Years	3269	21.08
	More than 85 Years	183	1.18
Gender	Female	24057	59.75
	Male	16204	40.25
Specialty of the reporters	Healthcare Professional	26057	51.10
	Consumer	24939	48.90
The most reported adverse events	Fatigue	5840	11.27
	Off-Label Use	4293	8.29
	Decreased Hemoglobin	3977	7.68
	Headache	3480	6.72
	Pyrexia	2418	4.67
	Death	2411	4.65
	Dyspnea	2141	4.13
	Nausea	1986	3.83
	Asthenia	1958	3.78
	Hemolysis	1859	3.59
	Decreased Platelet Count	1842	3.56
	Ineffective Drug	1747	3.37
	Increased Blood Lactate Dehydrogenase	1607	3.10
	Inappropriate Schedule of Product Administration	1592	3.07
	Abdominal Pain	1549	2.99
	Vomiting	1478	2.85
	Malaise	1475	2.85
	Pain	1442	2.78

Table 9.

The most reported adverse events of infliximab.

Variable	Category	Number of Cases	Percentage
Age	0-1 Month	412	0.30
	2 Months-2 Years	397	0.28
	3-11 Years	3549	2.57
	12-17 Years	11520	8.33
	18-64 Years	95613	69.13
	65-85 Years	26135	18.90
	More than 85 Years	677	0.49
Gender	Female	110278	62.26
	Male	66847	37.74
Specialty of the reporters	Healthcare Professional	159109	79.38
	Consumer	41338	20.62
The most reported adverse events	Off-Label Use	31802	15.68
	Ineffective Drug	30478	15.03
	Infusion Related Reaction	16247	8.01
	Aggravated Condition	15285	7.54
	Arthralgia	13706	6.76
	Rheumatoid Arthritis	13186	6.50
	Pain	13107	6.46
	Fatigue	11994	5.92
	Product Use Issue	10293	5.08
	Rash	9893	4.88
	Nausea	9829	4.85
	Intentional Product Use Issue	9758	4.81
	Crohn's Disease	9643	4.76
	Dyspnea	9479	4.68
	Headache	8732	4.31
	Diarrhea	8516	4.20
	Drug Intolerance	8440	4.16
	Alopecia	7887	3.89

Table 10.

The most reported adverse events of ipilimumab.

Variable	Category	Number of Cases	Percentage
Age	0-1 Month	4	0.01
	2 Months-2 Years	3	0.01
	3-11 Years	26	0.10
	12-17 Years	51	0.19
	18-64 Years	13493	49.76
	65-85 Years	13202	48.69
	More than 85 Years	335	1.24
Gender	Female	11591	35.85
	Male	20742	64.15
Specialty of the reporters	Healthcare Professional	31123	82.94
	Consumer	6400	17.06
The most reported adverse events	Death	3774	10.03
	Malignant Neoplasm Progression	3424	9.10
	Diarrhea	2895	7.69
	Colitis	2195	5.83
	Off Label Use	2017	5.36
	Pyrexia	1807	4.80
	Rash	1664	4.42
	Fatigue	1556	4.14
	Intentional Product Use Issue	1318	3.50
	Nausea	1254	3.33
	Hypophysitis	1023	2.72
	Pneumonia	1010	2.68
	Decreased Appetite	1003	2.67
	Vomiting	979	2.60
	Dyspnea	952	2.53
	Immune-Mediated Enterocolitis	921	2.45
	Adverse Event	897	2.38
	Pneumonitis	890	2.37

Table 11.

The most reported adverse events of nivolumab.

Variable	Category	Number of Cases	Percentage
Age	0-1 Month	18	0.03
	2 Months-2 Years	10	0.02
	3-11 Years	127	0.21
	12-17 Years	194	0.32
	18-64 Years	26898	44.82
	65-85 Years	31687	52.80
	More than 85 Years	1079	1.80
Gender	Female	25167	34.84
	Male	47065	65.16
Specialty of the reporters	Healthcare Professional	67151	81.08
	Consumer	15670	18.92
The most reported adverse events	Death	10807	13.01
	Malignant Neoplasm Progression	9042	10.89
	Off Label Use	4941	5.95
	Diarrhea	4438	5.34
	Fatigue	3554	4.28
	Intentional Product Use Issue	3269	3.94
	Pyrexia	3237	3.90
	Rash	2709	3.26
	Nausea	2655	3.20
	Decreased Appetite	2471	2.98
	Dyspnea	2443	2.94
	Pneumonia	2356	2.84
	Colitis	2014	2.42
	Pneumonitis	1968	2.37
	Asthenia	1806	2.17
	Hypothyroidism	1805	2.17
	Vomiting	1787	2.15
	Product Use in Unapproved Indication	1705	2.05

Table 12.

The most reported adverse events of omalizumab.

Variable	Category	Number of Cases	Percentage
Age	0-1 Month	90	0.24
	2 Months-2 Years	67	0.18
	3-11 Years	1007	2.69
	12-17 Years	1760	4.70
	18-64 Years	26229	70.05
	65-85 Years	7973	21.29
	More than 85 Years	315	0.84
Gender	Female	44918	73.10
	Male	16529	26.90
Specialty of the reporters	Healthcare Professional	36422	53.80
	Consumer	31276	46.20
The most reported adverse events	Asthma	9950	14.62
	Urticaria	8650	12.71
	Off-Label Use	8497	12.49
	Dyspnea	8467	12.44
	Ineffective Drug	6437	9.46
	Cough	5797	8.52
	Pruritus	5354	7.87
	Fatigue	5074	7.46
	Headache	4536	6.67
	Wheezing	4476	6.58
	Pneumonia	4299	6.32
	Malaise	4099	6.02
	Nasopharyngitis	3487	5.12
	Anaphylactic Reaction	3442	5.06
	Pain	3358	4.93
	Arthralgia	3249	4.77
	Hypersensitivity	3032	4.46

Table 13.

The most reported adverse events of palivizumab.

Variable	Category	Number of Cases	Percentage
Age	0-1 Month	1128	10.04
	2 Months-2 Years	10016	89.17
	3-11 Years	62	0.55
	12-17 Years	5	0.04
	18-64 Years	20	0.18
	65-85 Years	0	0.00
	More than 85 Years	1	0.01
Gender	Female	6695	43.10
	Male	8838	56.90
Specialty of the reporters	Healthcare Professional	9998	61.34
	Consumer	6300	38.66
The most reported adverse events	Respiratory Syncytial Virus Infection	2322	13.81
	Bronchiolitis	1893	11.26
	Pyrexia	1708	10.16
	Cough	1394	8.29
	Pneumonia	1191	7.08
	Death	1041	6.19
	Dyspnea	1038	6.17
	Vomiting	763	4.54
	Nasopharyngitis	660	3.92
	Product Dose Omission Issue	481	2.86
	Influenza	476	2.83
	Illness	456	2.71
	Diarrhea	455	2.71
	Bronchitis	452	2.69
	Apnea	403	2.40
	Asthma	379	2.25
	Nasal Congestion	378	2.25

Table 14.

The most reported adverse events of pembrolizumab.

Variable	Category	Number of Cases	Percentage
Age	0-1 Month	9	0.02
	2 Months-2 Years	13	0.02
	3-11 Years	27	0.05
	12-17 Years	78	0.14
	18-64 Years	24384	43.97
	65-85 Years	29764	53.67
	More than 85 Years	1178	2.12
Gender	Female	34453	48.90
	Male	36010	51.10
Specialty of the reporters	Healthcare Professional	63416	84.74
	Consumer	11416	15.26
The most reported adverse events	Malignant Neoplasm Progression	9216	12.26
	Death	4371	5.82
	Diarrhea	3809	5.07
	Product Use in Unapproved Indication	3705	4.93
	Fatigue	3523	4.69
	Off-Label Use	3092	4.11
	Pyrexia	2816	3.75
	Rash	2607	3.47
	Nausea	2401	3.19
	Decreased Appetite	2172	2.89
	Hypothyroidism	2091	2.78
	Hypertension	2050	2.73
	Interstitial Lung Disease	1907	2.54
	Asthenia	1821	2.42
	Pneumonitis	1783	2.37

Table 15.

The most reported adverse events of rituximab.

Variable	Category	Number of Cases	Percentage
Age	0-1 Month	78	0.07
	2 Months-2 Years	764	0.68
	3-11 Years	2252	2.00
	12-17 Years	2208	1.96
	18-64 Years	64413	57.25
	65-85 Years	43421	38.59
	More than 85 Years	1577	1.40
Gender	Female	82220	56.89
	Male	62316	43.11
Specialty of the reporters	Healthcare Professional	160660	86.35
	Consumer	25407	13.65
The most reported adverse events	Off-Label Use	35269	18.59
	Ineffective Drug	26789	14.12
	Rheumatoid Arthritis	15671	8.26
	Pain	13238	6.98
	Fatigue	12955	6.83
	Pneumonia	11303	5.96
	Arthralgia	10806	5.70
	Pyrexia	10450	5.51
	Infusion Related Reaction	10081	5.31
	Rash	9942	5.24
	Nausea	9576	5.05
	Drug Intolerance	8954	4.72
	Infection	8809	4.64
	Joint Swelling	8636	4.55
	Dyspnea	8616	4.54
	Contraindicated Product Administered	7932	4.18
	Intentional Product Use Issue	7818	4.12
	Neutropenia	7808	4.12

Table 16.

The most reported adverse events of secukinumab.

Variable	Category	Number of Cases	Percentage
Age	0-1 Month	22	0.04
	2 Months-2 Years	46	0.08
	3-11 Years	83	0.15
	12-17 Years	247	0.43
	18-64 Years	45580	79.89
	65-85 Years	10774	18.88
	More than 85 Years	303	0.53
Gender	Female	82987	61.09
	Male	52863	38.91
Specialty of the reporters	Healthcare Professional	53374	36.99
	Consumer	90912	63.01
The most reported adverse events	Ineffective Drug	26141	17.96
	Psoriasis	21468	14.75
	Pain	14103	9.69
	Arthralgia	13009	8.94
	Pruritus	8501	5.84
	Fatigue	8403	5.77
	Psoriatic Arthropathy	7854	5.40
	Rash	7231	4.97
	Inappropriate schedule of drug administration	7011	4.82
	Aggravated Condition	6637	4.56
	Nasopharyngitis	6488	4.46
	Diarrhea	6451	4.43
	Pain In Extremity	6210	4.27
	Malaise	6137	4.22
	Headache	5590	3.84
	Dose Omission Issue	5505	3.78

Table 17.

The most reported adverse events of tocilizumab.

Variable	Category	Number of Cases	Percentage
Age	0-1 Month	35	0.06
	2 Months-2 Years	175	0.34
	3-11 Years	1175	2.27
	12-17 Years	1117	2.15
	18-64 Years	31750	61.24
	65-85 Years	16782	32.37
	More than 85 Years	812	1.57
Gender	Female	64441	77.74
	Male	18457	22.26
Specialty of the reporters	Healthcare Professional	63724	68.22
	Consumer	29684	31.78
The most reported adverse events	Ineffective Drug	26475	28.14
	Rheumatoid Arthritis	16437	17.47
	Off-Label Use	15797	16.79
	Pain	14653	15.57
	Arthralgia	13446	14.29
	Joint Swelling	11928	12.68
	Fatigue	10711	11.38
	Rash	9725	10.34
	Drug Intolerance	8985	9.55
	Contraindicated Product Administered	8835	9.39
	Arthropathy	7372	7.83
	Swelling	7119	7.57
	Alopecia	7057	7.50
	Treatment Failure	7027	7.47
	Headache	6967	7.40
	Abdominal Discomfort	6886	7.32
	Synovitis	6827	7.26
	Hypersensitivity	6825	7.25

Table 18.

The most reported adverse events of trastuzumab.

Variable	Category	Number of Cases	Percentage
Age	0-1 Month	36	0.10
	2 Months-2 Years	26	0.07
	3-11 Years	10	0.03
	12-17 Years	9	0.03
	18-64 Years	25456	72.81
	65-85 Years	9213	26.35
	More than 85 Years	214	0.61
Gender	Female	43137	93.01
	Male	3243	6.99
Specialty of the reporters	Healthcare Professional	44946	83.72
	Consumer	8741	16.28
The most reported adverse events	Diarrhea	5406	9.92
	Nausea	3776	6.93
	Fatigue	3614	6.63
	Off-Label Use	3424	6.28
	Death	3249	5.96
	Disease Progression	3084	5.66
	Myelosuppression	2763	5.07
	Vomiting	2571	4.72
	Dyspnea	2498	4.58
	Pyrexia	2267	4.16
	Asthenia	2010	3.69
	Neutropenia	1941	3.56
	Decreased Ejection Fraction	1896	3.48
	Neuropathy Peripheral	1773	3.25
	Anemia	1599	2.93
	Rash	1555	2.85
	Alopecia	1502	2.76
	Headache	1489	2.73

Table 2.

The most reported adverse events of adalimumab.

Variable	Category	Number of Cases	Percentage
Age	0-1 Month	455	0.11
	2 Months-2 Years	229	0.06
	3-11 Years	2944	0.73
	12-17 Years	9237	2.29
	18-64 Years	303740	75.22
	65-85 Years	84702	20.98
	More than 85 Years	2470	0.61
Gender	Female	432161	67.84
	Male	204865	32.16
Specialty of the reporters	Healthcare Professional	180635	27.87
	Consumer	467532	72.13
The most reported adverse events	Ineffective Drug	78591	11.71
	Injection Site Pain	49940	7.44
	Arthralgia	44533	6.63
	Pain	42588	6.34
	Fatigue	34540	5.15
	Rheumatoid Arthritis	29313	4.37
	Headache	25863	3.85
	Nausea	24290	3.62
	Incorrect Dose Administered	23080	3.44
	Diarrhea	22966	3.42
	Rash	22866	3.41
	Psoriasis	22757	3.39
	Pain In Extremity	22193	3.31
	Crohn's Disease	20724	3.09
	Nasopharyngitis	19101	2.85
	Joint Swelling	18600	2.77
	Pyrexia	17279	2.57
	Device Issue	17191	2.56

Table 19.

The most reported adverse events of ustekinumab.

Variable	Category	Number of Cases	Percentage
Age	0-1 Month	62	0.13
	2 Months-2 Years	49	0.10
	3-11 Years	230	0.48
	12-17 Years	1113	2.34
	18-64 Years	37894	79.62
	65-85 Years	7920	16.64
	More than 85 Years	323	0.68
Gender	Female	43331	58.40
	Male	30862	41.60
Specialty of the reporters	Healthcare Professional	56729	67.51
	Consumer	27303	32.49
The most reported adverse events	Dose Omission Issue	12259	14.47
	Ineffective Drug	11145	13.15
	Off-Label Use	9769	11.53
	Psoriasis	5122	6.04
	Fatigue	4389	5.18
	Crohn's Disease	4371	5.16
	Arthralgia	3883	4.58
	Product Use Issue	3802	4.49
	Pain	3764	4.44
	Rash	3644	4.30
	Headache	3569	4.21
	Aggravated Condition	3386	4.00
	Infusion Related Reaction	3344	3.95
	Lower Respiratory Tract Infection	3188	3.76
	Pneumonia	3175	3.75
	Diarrhea	3077	3.63
	Alopecia	2875	3.39

Discussion

This study provides a detailed assessment of monoclonal antibody-related adverse event (AE) reports submitted to the FAERS database, focusing on the scale, patient demographics, implicated drug classes, and associated outcomes. Previous FAERS-based analyses have largely focused on single agents or specific adverse event categories rather than providing a cross-drug comparison. For example, Tang et al examined the safety profile of ixekizumab through disproportionality analysis, while Zhou et al focused specifically on thromboembolic events associated with antiangiogenic monoclonal antibodies.^12,13 In contrast, the current study adopts a broader descriptive approach across multiple monoclonal antibodies with diverse mechanisms of action, allowing for the identification of overarching reporting patterns rather than isolated safety signals. This broader perspective complements existing studies by highlighting similarities and differences in real-world reporting behavior across therapeutic classes.

The majority of adverse events were recorded in adults aged 18 to 64 years, which is consistent with the typical patient population treated with mAbs (e.g., autoimmune disorders, cancer). Healthcare professionals (HCPs) provided the bulk of reports for bevacizumab (84.90%), daratumumab (92.18%), and pembrolizumab (84.74%), most likely due to their use in hospital settings for complicated illnesses such as cancer. Consumer-reported adverse events were higher for adalimumab (72.13%) and dupilumab (20.97%), probably due to self-administration and continuous use in outpatient settings.

Gender-related differences were evident across the analyzed medications. Female predominance was observed for adalimumab (67.84%), dupilumab (61.15%), and tocilizumab (77.74%), which may reflect the higher prevalence of autoimmune diseases among women. In contrast, a male predominance was noted for cetuximab (67.09%), ipilimumab (64.15%), and nivolumab (65.16%), consistent with the generally higher incidence of certain cancers in men. Palivizumab accounted for the highest proportion of pediatric reports, with 89.17% occurring in infants aged 2 months to 2 years, reflecting its established role in the prevention of respiratory syncytial virus (RSV) infection among high-risk neonates and infants. These findings are consistent with previous studies. Sisi et al reported that adverse event (AE) reports for all evaluated drugs were predominantly submitted for female patients, with the highest proportion observed for belimumab (94.91%). The authors attributed this pattern to the primary indication of belimumab for systemic lupus erythematosus (SLE), a condition that disproportionately affects women. Likewise, rheumatoid arthritis (RA), a major indication for several agents included in the present study, such as adalimumab, etanercept, and rituximab, exhibits a female-to-male ratio of approximately 2–3:1. ¹⁴ Similarly, Zhou et al found that the majority of AE reports associated with ramucirumab and aflibercept involved males aged 65 years and older. In contrast, bevacizumab-related reports were distributed across a broader age range and included a higher proportion of women, likely due to its extensive use in multiple malignancies, including ovarian cancer. ¹³ However, after excluding ovarian cancer cases, the sex distribution of bevacizumab reports (female, 35.3%; male, 42.0%) became comparable to those observed for ramucirumab and aflibercept. Furthermore, Tang et al reported a predominance of female patients among ixekizumab-associated adverse event reports in the FDA Adverse Event Reporting System (FAERS), with 14,877 reports involving females compared with 9,689 involving males. ¹²

According to the current study, the most commonly reported adverse events (AEs) linked to monoclonal antibodies include: gastrointestinal disturbances (e.g., nausea, vomiting, diarrhea); infections & immune suppression (e.g., pneumonia, upper respiratory infections); musculoskeletal & joint-related AEs (e.g., arthralgia and rheumatoid arthritis flare); hematologic & laboratory abnormalities (e.g., neutropenia, thrombocytopenia, and anemia); injection/administration problems (e.g., injection site pain and incorrect dosing/omission issues); and serious & fatal outcomes (e.g., death and disease progression). Catapano and Papadopoulos noted that while monoclonal antibodies (mAbs) are generally well tolerated, they can still lead to adverse events (AEs). Many of these AEs are target-dependent, varying based on the antibody’s mechanism and therapeutic application. ¹⁵ Baldo highlighted that despite their precise targeting—which minimizes harm to healthy cells—mAbs can still trigger hypersensitivity reactions, including types I (anaphylaxis, urticaria), II (e.g., hemolytic anemia, early-onset neutropenia), III (serum sickness, pneumonitis), and IV (Stevens-Johnson syndrome, toxic epidermal necrolysis). Additionally, they may cause cutaneous, pulmonary, cardiac, and hepatic complications. ¹⁶ Severe infusion reactions resembling anaphylaxis can occur, along with rare but potentially life-threatening systemic syndromes, often linked to cytokine release and inflammatory responses. Notably, epidermal growth factor receptor (EGFR)-targeted antibodies may induce non-immune-mediated papulopustular and mucocutaneous eruptions. ¹⁶ Htet et al found that mAb therapy in COVID-19 patients was associated with a higher risk of hepatotoxicity and neutropenia compared to standard treatments or placebo, based on moderate-certainty evidence. ⁵ Maksymowicz and Podhorecka reported that mAbs, whether used alone or in combination, have become a key treatment for hematologic malignancies, improving survival rates and prognosis. However, their anticancer benefits come with side effects. The most frequent are infusion-related reactions (IRRs), typically occurring within hours of administration due to cytokine release. These reactions are usually mild to moderate, presenting as rash, fever, nausea, vomiting, dizziness, headache, hypotension, or tachycardia. Other common toxicities include cytopenias, which increase infection and bleeding risks. ¹⁷

Reporting adverse drug events by healthcare professionals and consumers is crucial. When physicians diligently identify and report these events, they can contribute to updates in drug labeling or safety alerts, ultimately improving prescribing practices and safeguarding public health. While busy physicians may hesitate to report adverse events, the reasons for doing so are equally compelling. With the rise of polypharmacy across all age groups, along with the growing availability of alternative remedies and over-the-counter medications, the importance of reporting drug side effects cannot be overstated. ¹⁸ Sienkiewicz et al noted that legislation introduced in recent years enabled patients, their legal representatives, and caregivers to report adverse drug reactions (ADRs), making them a valuable supplementary source of safety data. ¹⁹

Although the present study focused primarily on descriptive characterization of FAERS reports, some differences across monoclonal antibodies were observed. Agents used for autoimmune diseases, such as adalimumab, secukinumab, and ustekinumab, demonstrated higher proportions of dermatologic and musculoskeletal adverse events. These patterns are consistent with, though not confirmatory of, the known pharmacological profiles of these agents. In contrast, oncology-related monoclonal antibodies such as nivolumab, pembrolizumab, and ipilimumab showed higher reporting of serious outcomes, including death and disease progression, likely reflecting the severity of the treated malignancies rather than direct drug toxicity. Several reported events, particularly death and malignant disease progression associated with oncology-related monoclonal antibodies such as nivolumab, pembrolizumab, and ipilimumab, likely reflect the underlying severity of the treated malignancies rather than direct drug toxicity. Therefore, these findings should not be interpreted as causal safety signals. The differences in reported event proportions across monoclonal antibodies reflect variations in reporting behavior and should not be interpreted as differences in actual risk or incidence.

A major interpretive challenge in cross-drug comparisons is confounding by indication. Drugs used for life-threatening malignancies (e.g., nivolumab, pembrolizumab) are expected to have higher rates of serious outcomes, not because they are more toxic, but because the underlying diseases are more severe. Similarly, the higher female representation in autoimmune mAbs reflects the epidemiology of those conditions, not a drug-specific effect on women.

Although patient reporting enhances pharmacovigilance systems, significant efforts are still needed to improve ADR reporting among patients, particularly in raising awareness of their right to report and their potential impact on improving health outcomes for others. Further research could explore how factors such as drug category, dosage form, therapeutic indications, or ADR severity influence reporting rates among both patients and healthcare professionals. Such insights could help develop more effective strategies to encourage patient participation in ADR reporting.

Limitations

FAERS is a spontaneous reporting database and has inherent limitations. The data are subject to underreporting, reporting bias, and incomplete clinical information. Because FAERS lacks accurate exposure denominators (i.e., the total number of patients receiving a drug), the database cannot be used to calculate incidence rates of adverse events. Additionally, causal relationships between the reported drug and adverse event cannot be confirmed due to potential confounding factors, including underlying disease severity, concomitant medications, and confounding by indication. Moreover, the study did not stratify adverse events by therapeutic indication, treatment duration, or time trends across reporting years. These analyses could provide additional insights into changing pharmacovigilance patterns and should be explored in future studies.

Additionally, reporting patterns in FAERS may be influenced by the Weber effect, where adverse event reporting increases shortly after drug approval and subsequently declines. Polypharmacy and confounding by indication may also affect reported drug–event associations, particularly in patients with complex conditions such as malignancies or autoimmune diseases. Disproportionality analyses such as reporting odds ratios (ROR) or proportional reporting ratios (PRR) are commonly used in pharmacovigilance studies to identify potential safety signals. However, the present study focused on descriptive characterization of reported events across monoclonal antibodies rather than signal detection. Future research using formal disproportionality analyses could provide additional pharmacovigilance insights.

Conclusion

This descriptive analysis of FAERS data identified frequently reported adverse events, demographic patterns, and reporting characteristics associated with 18 monoclonal antibody therapies. Administration issues, product-use problems, and drug-ineffectiveness perceptions were among the most commonly documented reports. These findings should be interpreted cautiously, as spontaneous reporting data cannot establish causal relationships, and reported proportions do not reflect true incidence rates or comparative risk. Differences across drug classes likely reflect confounding by indication, underlying disease severity, and variation in reporting behavior rather than true pharmacological differences. These reporting patterns may generate hypotheses for future controlled pharmacovigilance or epidemiologic studies examining whether specific adverse event clusters warrant targeted clinical investigation. Future research should prioritize prospective cohort studies and active surveillance systems to quantify true incidence rates, identify at-risk subpopulations, and evaluate whether class-specific or drug-specific safety signals observed in spontaneous reporting translate into clinically meaningful risks under controlled conditions.

ORCID iD

Nehad Jaser Ahmed https://orcid.org/0000-0003-4215-6225

Ethical Considerations

This study used publicly available, de-identified data from the FDA Adverse Event Reporting System (FAERS). Therefore, Institutional Review Board approval and informed consent were not required.

Data Availability Statement

The datasets used and/or analyses during the current study are available from the corresponding author upon reasonable request.*