Age-Specific Differences in Omalizumab-Related Adverse Drug Reaction Signals between Children and Adults: An Analysis Based on the FAERS Database

Age-Specific Differences in Omalizumab-Related Adverse Drug Reaction Signals between Children and Adults: An Analysis Based on the FAERS Database | 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 Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed.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. 5 March 2026 V1 Latest version Share on Age-Specific Differences in Omalizumab-Related Adverse Drug Reaction Signals between Children and Adults: An Analysis Based on the FAERS Database Authors : Hairui Zheng 0009-0007-1470-2256 , Lu Liang , Ning Li , and Yi Su [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.177270317.73494041/v1 116 views 59 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Objective：To analyze age-specific differences in post-marketing adverse drug reaction (ADR) signals of omalizumab between children (<18 years) and adults (≥18 years) using FAERS data, to inform optimized medication safety monitoring strategies. Methods：Omalizumab-related ADR reports (2003Q1–2025Q3) were extracted from FAERS and stratified by age. ADRs were coded with MedDRA. Signals were mined using four disproportionality methods (ROR, PRR, BCPNN, MGPS), with validity requiring all thresholds met. Cumulative incidence and time-to-onset (TTO) were analyzed. Results：Among 62,925 reports (4% children, 45% adults), both groups showed strong signals for respiratory/immune disorders. Children had an additional musculoskeletal signal; adults had more general disorders. At PT level, adults had broader coverage (allergic/infectious signals), while children had narrower coverage with a unique strong signal for asthmatic crisis (ROR=52.83). Children had shorter median TTO (34.4 vs 63.1 days) and faster cumulative incidence; adults had longer late-onset risk. Conclusion：Omalizumab shows significant age-specific ADR differences. Individualized monitoring strategies are needed to enhance clinical safety. Introduction Omalizumab is a humanized monoclonal antibody that effectively alleviates allergic reactions 1–3 by specifically binding to free immunoglobulin E (IgE), blocking its interaction with surface receptors on mast cells and eosinophils, and inhibiting the release of inflammatory mediators. As the first biological agent endorsed by the Global Initiative for Asthma (GINA) for the treatment of IgE-mediated severe allergic asthma 4 , it was approved by the U.S. FDA in 2003 for the treatment of moderate-to-severe allergic asthma in children aged 6 years and older and adults 5 . Subsequently, its indications have gradually expanded to include chronic urticaria in patients aged 12 years and older 6 and adult nasal polyps 7 , with further approval for the treatment of IgE-mediated food allergy in 2024 8 . It has also demonstrated favorable efficacy in various other allergic conditions, such as allergic rhinitis 9 and atopic dermatitis 10 . With the continuous expansion of its clinical applications 11 , particularly its extended use in children, the medication safety of omalizumab has garnered increasing attention. From the perspective of developmental pharmacology, there are significant differences in the drug exposure-response relationship between children and adults, leading to population-specific characteristics in the type and incidence of ADRs 12 . Current studies on omalizumab-related ADRs are mostly based on clinical trials and meta-analyses. Although common ADRs such as headache, injection site reactions, and arthralgia have been identified 6,13,14 , these studies are limited by small sample sizes and strict inclusion criteria, making it difficult to fully reflect the real-world medication safety profile. More importantly, there is a lack of systematic analysis on the differences between children and adults. Traditional ADR signal detection algorithms are mostly based on the entire population, which tend to overlook the unique medication risks in children. Given that children’s physiological functions are not yet fully developed, their tolerance to drugs is inherently different from that of adults 12 . Clarifying the differences in ADR signals between the two populations is therefore crucial for clinical medication safety. The FDA Adverse Event Reporting System（Faers） serves as a core tool for post-marketing drug safety monitoring 15 , continuously collecting real-time ADR data submitted by healthcare professionals, consumers, and other stakeholders. It offers advantages such as a large sample size, frequent updates, and high data accessibility, providing reliable data support for real-world drug safety research 16 . In view of this, the present study systematically analyzed the differences in omalizumab-related ADR signals between children and adults based on reports from the FAERS database spanning from the first quarter of 2003 to the third quarter of 2025, aiming to explore the occurrence characteristics and specific risks of ADRs in different populations. This study intends to provide a scientific basis for clinicians to accurately monitor medication risks in different age groups and formulate individualized medication plans, optimize the clinical risk management strategy of omalizumab, and promote the rational use of drugs and safety assurance for both children and adult patients. Materials and methods 1. Data Source Publicly available data were retrieved from the Faers(https://www.fda.gov/drugs/development-approval-process-drugs/drug-approvals-and-databases), a spontaneous pharmacovigilance reporting database. No ethical approval was required, and all analyses adhered to the Declaration of Helsinki. Data spanning Q1 2003 to Q3 2025 were extracted, covering omalizumab’s full post-marketing period. 2. Data Cleaning and Stratification ADR reports with omalizumab as the primary suspected drug were identified using its generic name (Omalizumab), original brand (Xolair), and biosimilar (Omlyclo). All ADRs were coded into System Organ Classes (SOCs) and Preferred Terms (PTs) per the Medical Dictionary for Regulatory Activities (MedDRA, Version 26.0). Duplicate reports and those missing key variables (age, ADR description) were excluded to ensure data quality. The cleaned dataset was stratified into two age subgroups: children (<18 years) and adults (≥18 years). Python and MySQL were used for data processing, merging and management to guarantee integrity and consistency. 3. ADR Signal Detection Analysis ADR signal detection was performed via disproportionality analysis, a widely used approach for alertness analysis in large spontaneous reporting databases that preliminarily evaluates potential drug-ADR causal associations (requiring subsequent comprehensive clinical case validation) 17 . This method quantifies discrepancies by comparing observed and expected report counts for specific drug-adverse event combinations 18 . Four internationally recognized disproportionality methods were integrated for signal detection: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) 19 . A positive signal was defined only by simultaneous fulfillment of all thresholds: • ROR: 95% confidence interval (CI) lower bound > 1 • PRR: > 2 with χ² ≥ 4 • BCPNN: Information Component (IC) 95% CI lower bound > 0 • MGPS: Empirical Bayes Geometric Mean (EBGM) 95% CI lower bound > 1 This integrated multi-method approach reduced false positive signals, enhanced the reliability of drug-ADR association detection, and ensured robust drug safety assessment. 4. TTO Analysis and Weibull Distribution Modeling Time-to-onset (TTO) was defined as the interval from initial omalizumab administration to the first reported ADR. For reports with missing exact onset dates, the midpoint of the reported time window was imputed for TTO calculation. Cumulative ADR incidence over time was estimated by the Kaplan-Meier method, with intergroup TTO distribution differences compared via the log-rank test. Parametric survival analysis using the Weibull distribution model characterized ADR onset temporal dynamics—this model was selected for its flexibility in capturing variable hazard rates, making it well-suited for describing post-marketing ADR onset patterns. Key Weibull distribution parameters were defined as follows: Shape parameter (β): Reflects the ADR hazard rate trend (β 1 = increasing hazard rate) Scale parameter (α, characteristic life): Time point at which 63.2% of ADRs occurred in the study population All statistical analyses were performed in Python (Version 3.9) with the lifelines library for survival analysis and Weibull regression modeling. A two-sided p -value < 0.05 was considered statistically significant for all analyses. Results 1. ADR reports Omalizumab-related ADR reports were systematically processed and analyzed using three core FAERS datasets: demographic (DEMO), drug exposure (DRUG), and adverse event (REAC) files. Initial DEMO records (23,488,769) were de-duplicated to 19,586,570 unique entries, which were then linked with DRUG (71,482,606) and REAC (58,226,317) records to integrate demographic, medication, and adverse event data (Fig. 1). Two cohorts of omalizumab as the primary suspected drug were screened from the integrated dataset: omalizumab-related ADR reports ( n =62,925) and omalizumab-induced ADR reports ( n =251,695). These reports were stratified by age (<18 years, children; ≥18 years, adults). Among the 62,925 omalizumab-related ADR reports, 2,792 (4%) were in children, 28,075 (45%) in adults, and 32,057 (51%) had missing age data (Fig. 2). Stratified reports were subjected to ADR signal mining via four disproportionality methods (ROR, PRR, BCPNN, MGPS), with subsequent drug safety analysis across four dimensions: clinical indications, outcome events and incidence, ADR time-to-onset (TTO), and population clinical characteristics. Fig.1. The process of selecting omalizumab-associated ADRs from FAERS database. Fig.2. Age Group Distribution of Omalizumab-Related ADRs Reports The 62,925 omalizumab-related ADR reports extracted from FAERS (Q1 2003–Q3 2025) exhibited a steady year-on-year growth (Fig. 3), consistent with the expanded clinical indications and increased utilization of omalizumab 11 . Key demographic and reporting characteristics of the pediatric and adult subgroups are summarized in Table 1. Gender distribution was imbalanced in adults (females: 20,537, 73.15%; males: 7,296, 25.99%) but balanced in children (females: 1,380, 49.43%; males: 1,308, 46.85%). Geographically, the United States contributed the majority of reports (65.63% in children, 64.92% in adults). Physician-reported cases predominated in the pediatric subgroup (1,216, 43.55%), while consumer-initiated reports were the most common in adults (12,190, 43.42%). Fig.3. The annual distribution of omalizumab-related ADRs reports from 2004 to 2025 Table 1 Characteristics of ADRs reports on omalizumab in children and Adults. Total 2792 28075 Gender Female 1380(49.43%) 20537(73.15%) Male 1308(46.85%) 7296(25.99%) Missing 104(3.72%) 242(0.86%) The top 10 Reporting Country United States 1625(65.63%) 16443(64.92%) Canada 344(13.89%) 5701(22.51%) Switzerland 93(3.76%) 758(2.99%) Japan 112(4.52%) 559(2.21%) France 88(3.55%) 487(1.92%) Brazil 37(1.49%) 378(1.49%) United Kingdom 47(1.90%) 293(1.16%) Colombia 75(3.03%) 259(1.02%) Argentina 24(0.97%) 229(0.90%) Germany 31(1.25%) 220(0.87%) Outcome Other Serious 951(34.06%) 10673(38.02%) Hospitalization 586(20.99%) 5770(20.55%) Life-Threatening 98(3.51%) 846(3.01%) Disability 43(1.54%) 383(1.36%) Death 24(0.86%) 1007(3.59%) Congenital Anomaly 23(0.82%) 12(0.04%) Required Intervention to Prevent Permanent Impairment/Damage 14(0.50%) 128(0.46%) Missing 175(6.27%) 1472(5.24%) Reporter Type Consumer 910(32.59%) 12190(43.42%) Physician 1216(43.55%) 10060(35.83%) Other health-professional 290(10.39%) 2384(8.49%) Pharmacist 69(2.47%) 846(3.01%) Lawyer 1(0.04%) 2(0.01%) Others 279(9.99%) 2312(8.24%) Missing 27(0.97%) 281(1.00%) 2. Signal mining at the SOC level Adult subgroup ADR signals featured high report volumes concentrated in core organ systems (Fig. 4a). General disorders and administration site conditions had the highest report count (28,099) but only a mild positive signal (ROR=1.11, 95% CI 1.09–1.12), reflecting a weak drug association and likely attributable to the large treated population and prolonged exposure. In contrast, Respiratory, thoracic and mediastinal disorders (27,558 cases; ROR=3.78, 95% CI 3.73–3.83) and Immune system disorders (5,517 cases; ROR=3.33, 95% CI 3.24–3.42) were strong positive signals, with markedly elevated RORs, narrow 95% CIs, and high PRR χ² values (48,711.11 and 8,544.34, respectively), confirming these as core drug-related ADR target systems with robust statistical reliability. Moderate positive signals (ROR 1.41–1.60) were additionally observed for Infections and infestations, Skin and subcutaneous tissue disorders, and Ear and labyrinth disorders, indicating a significantly elevated ADR risk relative to the database background. Children subgroup ADR signals exhibited age-specific high association strength (Fig. 4b). Notably, General disorders and administration site conditions was the most frequently reported SOC and also a moderate positive signal (ROR=1.56, 95% CI 1.46–1.62)—a stark contrast to the adult subgroup’s high report volume but weak drug association for this SOC, likely due to children organisms’ increased sensitivity to local/systemic stimulation by biological agents. Consistent with adults, Respiratory, thoracic and mediastinal disorders (ROR=3.77, 95% CI 3.59–3.97) and Immune system disorders (ROR=3.36, 95% CI 1.13–7.70) were strong positive signals in children. This shared feature derives from omalizumab’s pharmacological mechanism (specific binding to free IgE and downregulation of high-affinity IgE receptors), rendering respiratory and immune system abnormalities age-independent class-effect ADRs of this drug. Uniquely, the children subgroup also had positive signals for Musculoskeletal and connective tissue disorders (ROR=1.38, 1.20), with no valid signals detected for this SOC in adults; this age-specific difference may be linked to the physiological characteristics of the developing children musculoskeletal system. SOC-level signal characteristics confirmed omalizumab’s inherent safety profile and defined age-specific monitoring priorities: both age groups require priority monitoring for respiratory and immune system ADRs. Adults need surveillance for high-incidence general and administration site disorders, while children require additional vigilance for musculoskeletal discomfort. No valid signals were detected for Nervous system disorders and Cardiac disorders in either subgroup, indicating relatively controllable safety for these systems and allowing for reduced unnecessary monitoring burden. Fig.4. Forest plot of SOC level signal detection in Adults(a) and Children (b) 3. Signal mining at the PT level A total of 4,674 Preferred Terms (PTs) were reported for omalizumab-related ADRs in the adult subgroup, compared with 1,504 PTs in the children subgroup. PT signal reliability was verified using four pharmacovigilance algorithms (ROR, PRR, MGPS, BCPNN), with Venn diagrams visualizing the overlap of positive signals identified by each method. Multi-algorithm signal detection showed markedly higher consistency in adults (Fig. 5a): MGPS identified 159 unique positive signals, MGPS and BCPNN had 373 intersecting signals, and 96 core consensus signals were recognized by all four algorithms; ROR and PRR additionally had 63 intersecting signals. This high consistency reflected the high stability of adult ADR signals, attributable to the large treated population and sufficient ADR report volume in this subgroup. In stark contrast, multi-algorithm consistency was significantly reduced in the children subgroup (Fig. 5b): MGPS identified only 119 unique signals, MGPS and BCPNN had 141 intersecting signals, and merely 12 consensus signals were confirmed by all four algorithms; ROR and PRR identified just 2 and 3 unique signals, respectively. This low consistency was closely associated with the small children treated population and limited ADR report volume, which caused greater signal intensity fluctuations and increased discrepancies in algorithmic detection results. Fig.5. Venn Diagram of PT Signals Meeting the Criteria of Four Algorithms in Adults (a) and Children(b) Systematic analysis of omalizumab-related ADR SOC-PT hierarchical mapping revealed significant age-specific differences in PT coverage, composition, and SOC-PT association patterns between the two subgroups. Adult PTs exhibited a broad-coverage, multi-type distribution (Fig. 6a), with a large number of outer-layer PTs and dense, diverse PT connections for each core SOC—for example, Respiratory, thoracic and mediastinal disorders included asthma, dyspnea, cough and wheezing, while other core SOCs also had varied PT manifestations. Children PTs showed a narrow-focus, low-type distribution (Fig. 6a), with limited overall coverage and sparse SOC-PT connections; only core SOCs (e.g., respiratory and general/administration site disorders) were associated with a small number of key PTs. Age-related differences in PT profile composition were particularly prominent (Fig. 6b). Adult PTs were dominated by allergic skin reactions and infectious manifestations (e.g., urticaria, pruritus, atopic dermatitis, pneumonia, sinusitis), with unique PTs including elevated blood immunoglobulin E, chronic airway obstruction and chronic sinusitis. Children PTs showed distinct age specificity, focusing on local administration site reactions and acute severe respiratory manifestations (e.g., asthmatic crisis, injection site pain/erythema/induration, growing pains)—all unique to the children subgroup. Fig.6. Hierarchical Mapping of ADRs in Adults(a) and Children(b) PT-level signal forest plots showed that in adults (Fig. 7a), the most frequently reported PTs were asthma (4,185 cases; ROR=17.08, 95% CI:16.54–17.63) and urticaria (3,745 cases; ROR=9.17, 95% CI:8.87–9.48), with IC values in the high range of 3.11–3.96. These PTs represented core drug-related ADRs in adults, with high occurrence rates and strong drug associations. Additional significant signals included respiratory PTs (dyspnea, cough) and allergic PTs (pruritus), while a small number of PTs (dizziness, pain) were non-significant, with no clear drug association. In the children subgroup (Fig. 7b), core PT signals exhibited significantly higher intensity: asthma had an ROR of 21.33 (95% CI:19.26–23.63) and an IC value of 4.22, indicating a closer drug-ADR association in children. Notably, the children subgroup had a unique strong positive signal—asthmatic exacerbation (ROR=52.80, 95% CI:40.77–68.45; IC=5.36), a severe adverse event requiring heightened clinical vigilance following omalizumab administration. Administration site reaction-related PTs (e.g., injection site pain) were also significant signals, consistent with children physiological sensitivity to local stimulation. In contrast, PTs such as vomiting and erythema were non-significant in children, a notable difference from the adult signal distribution. Omalizumab PT-level signals shared key commonalities across age groups while displaying distinct age-specific differences. Commonalities included strongly significant signals for respiratory and allergy-related PTs (e.g., asthma, urticaria), reflecting inherent ADRs linked to the drug’s IgE-targeted pharmacological mechanism. Key differences were: markedly higher signal intensity and unique high-risk PTs (e.g., asthmatic crisis) in children; and high-report-volume allergic and infectious reactions in adults. These findings inform clinical monitoring priorities: adults require focused surveillance for high-frequency allergic and respiratory ADRs, while children need enhanced vigilance for asthmatic exacerbation and local administration site reactions. Collectively, these age-specific PT-level differences arise from the interaction between omalizumab’s pharmacological effects and the physiological characteristics and disease spectra of different age groups, providing a clear direction for developing targeted, age-specific medication safety monitoring strategies. Fig.7. Forest plot of PT level signal detection in Adults(a) and Children(b) 4. Cumulative Incidence of ADRs and Weibull Distribution of Onset Time ADR cumulative incidence was calculated and Weibull distribution models were fitted for both subgroups, with resultant curves showing a typical pattern of rapid initial rise followed by a gradual plateau in both adults and children patients (Fig. 8a, b). The children subgroup exhibited a steeper ascending rate, with cumulative incidence exceeding 90% within the first 1000 days of omalizumab administration, compared with ~85% in adults at the same time point—indicating a more rapid exposure response and higher early-stage ADR risk in children. The children curve also reached a plateau earlier (~3000 days) versus adults (~6000 days), reflecting a more concentrated ADR onset time window in children and a more persistent late-onset risk in adults. A combined population comparison curve further highlighted these temporal disparities (Fig. 8c): the children curve consistently lay above the adult curve, with the most prominent gap within the first 2000 days. By day 2000, children cumulative incidence approached 100%, compared with only ~95% in adults. This difference is attributable to the immature immune system of children patients, driving more pronounced acute responses to drug exposure, while adult late-onset risk aligns with their higher burden of chronic comorbidities and longer durations of omalizumab exposure. Weibull fitting confirmed an early-onset, concentrated ADR pattern in children and a delayed-onset, persistent pattern in adults, defining clear temporal targets for phase-specific clinical monitoring: intensive surveillance for children patients within the first 1000 days, and balanced early monitoring and long-term late-onset risk control for adults Fig.8. Cumulative Incidence of ADRs Adults(a) and Children(b); Comparison of Cumulative Incidence of ADRs in Children and Adults(c) Time-to-onset (TTO) was further analysed via Weibull distribution parameters. The shape parameter β was 0.44 (95% CI: 0.44–0.45) in adults and 0.43 (95% CI: 0.42–0.45) in children patients, with both values <1—demonstrating a rapidly decreasing ADR risk over time and identifying the early post-administration period as a high-risk window for both groups. Further comparisons revealed significant TTO differences: the children subgroup had a markedly shorter median TTO (34.4 days, IQR: 1.0–216.0 days) than adults (63.1 days, IQR: 2.0–343.0 days). The children characteristic life (scale parameter α) was also much shorter (80.03 days) versus adults (143.85 days), reflecting a more concentrated ADR onset window and more prominent early risk in children. Density curve peak values confirmed this feature (Fig. 9a, b): the children peak density was ~0.0040, significantly higher than the adult value of 0.0025, indicating a higher ADR occurrence density and more concentrated early risk (0–100 days post-administration) in children patients. These temporal differences establish definitive age-specific targets for clinical medication safety management: children patients require enhanced ADR monitoring within the first 34 days to address concentrated early-stage risk, while adults need to balance early surveillance within the first 63 days with long-term control of late-onset ADR risk, thereby improving the precision of omalizumab safety monitoring across age groups. Fig.9. Weibull Distribution Analysis of ADRs Onset Time in Adults(a) and Children(b) Discussion Omalizumab’s efficacy and safety have been validated in rigorous pre-marketing clinical trials, yet the expansion of its indications, growing target population, and the heterogeneity of real-world patient characteristics have left the age-specific profiles of its adverse drug reactions (ADRs) incompletely elucidated. This study addressed this knowledge gap by systematically investigating and comparing omalizumab-related ADR signals in children patients (<18 years) and adults (≥18 years) using four internationally recognized disproportionality analyses (ROR, PRR, BCPNN, MGPS) on real-world FAERS data spanning Q1 2003 to Q3 2025. For the first time, we characterized age-specific ADR differences across SOC, PT, TTO, and cumulative incidence—filling the limitation of prior research that focused on the overall population without in-depth age-stratified analysis, and providing an evidence-based foundation for individualized medication safety monitoring strategies across age groups. A total of 62,925 omalizumab-related ADR reports were identified, with 4% (2,792) in children patients, 45% (28,075) in adults, and 51% with missing age data. This missingness reflects an inherent limitation of spontaneous reporting systems, and the results should therefore be interpreted with caution. Population characteristic analysis revealed a marked female predominance in adult ADR reports (73.15% female vs. 25.99% male), whereas gender distribution was balanced in children patients (49.43% female vs. 46.85% male). This disparity aligns with the epidemiological features of omalizumab’s core indications (asthma, chronic urticaria), which have a higher prevalence in females 20 , and female sex hormones may further exacerbate immune and inflammatory responses to increase ADR risk 21 . In contrast, gender-related physiological differences are not fully manifested in childhood, resulting in no significant gender bias in children ADR reports. Notable differences were also observed in report sources: physician-submitted reports predominated in children patients (43.55%), while consumer-initiated reports were the most common in adults (43.42%). This reflects the strict physician oversight of children medication use, with ADRs primarily monitored and reported by healthcare professionals, whereas adults have greater self-reporting capacity and lower reporting barriers—potentially introducing more subjective bias into adult ADR reports, which warrants careful clinical validation of corresponding signals. The annual distribution of omalizumab-related ADR reports showed a continuous upward trend from 2004 to 2025, with accelerated growth after 2018, directly attributable to the expansion of its indications to include food allergy 8 , allergic rhinitis 9 , and atopic dermatitis 10 , among other allergic conditions. At the SOC level, omalizumab-related ADR signals exhibited shared core features and age-specific characteristics in the two groups. Both children and adult patients had strong positive signals for Respiratory, thoracic and mediastinal disorders (adults: ROR=3.78; children: ROR=3.77) and Immune system disorders (adults: ROR=3.33; children: ROR=3.36)—a shared feature rooted in omalizumab’s core pharmacological mechanism of specific free IgE binding and inhibition of mast cell/eosinophil activation 1-3 . As the primary target organs of IgE-mediated diseases, the respiratory and immune systems are associated with age-independent class-effect ADRs of this drug. For General disorders and administration site conditions, adults had the highest report volume (28,099 cases) but only a mild positive signal (ROR=1.11), indicating these reactions are mostly cumulative events from a large treated population and prolonged exposure, with weak direct drug association. In contrast, this SOC was the most frequently reported in children patients and a moderate positive signal (ROR=1.56), reflecting the heightened sensitivity of immature children organisms to local and systemic stimulation by biological agents 12 . A unique children signal was also observed for Musculoskeletal and connective tissue disorders (no valid signals in adults), potentially linked to the physiological development of the children musculoskeletal system and indirect effects of omalizumab’s immunomodulation—further highlighting age-specific ADR profiles. PT-level signals further underscored omalizumab’s age-specific ADR characteristics. Adults had broad PT coverage (4,674 terms) dominated by allergic skin reactions and infectious manifestations (e.g., asthma: 4,185 cases, ROR=17.08; urticaria: 3,745 cases, ROR=9.17), a feature associated with their large treated population, prolonged drug exposure, and higher burden of chronic comorbidities that increase infection risk. Children patients had narrow PT coverage (1,504 terms) focused on local administration site reactions and acute severe respiratory manifestations, with asthmatic crisis as a unique strong positive signal (ROR=52.83, IC=5.36). This finding aligns with children physiological characteristics of immature immune development and prominent airway hyperreactivity 22 , indicating a significantly higher risk of acute asthma exacerbation in children following omalizumab administration. Weibull distribution analysis of ADR cumulative incidence and TTO revealed consistent temporal patterns of rapid initial rise followed by a gradual plateau in both groups, with distinct age-specific dynamics. Children patients had a steeper cumulative incidence rise (≥90% within 1,000 days vs. ~85% in adults), a significantly shorter median TTO (34.4 vs. 63.1 days), and a shorter characteristic life (α=80.03 vs. 143.85 days in adults). The children peak ADR incidence density (0.0040) within the first 100 days was also markedly higher than that in adults (0.0025), confirming a more concentrated ADR onset window and prominent early-stage risk in children. In contrast, adults had a later plateau in cumulative incidence (~6,000 days vs. 3,000 days in children), reflecting persistent late-onset ADR risk—consistent with their higher rates of chronic comorbidities, polypharmacy, and longer omalizumab exposure 23 . These temporal differences define clear phase-specific clinical monitoring targets: intensive surveillance for children patients within the first 34 days (median TTO), with enhanced control of acute reactions in the first 100 days; for adults, a balance of early monitoring within the first 63 days and long-term follow-up to detect late-onset chronic ADRs. The age-specific ADR differences of omalizumab are fundamentally driven by the interaction between its pharmacological effects and the physiological characteristics and disease spectra of different age groups. First, children patients have immature hepatic and renal function, impaired drug metabolism and excretion, and a developing immune system with a high proportion of naive immune cells 22 —rendering them more susceptible to drug accumulation and acute inflammatory or local stimulatory reactions to omalizumab’s immunomodulation. Adults, by contrast, have stable immune cell composition and stronger adaptive capacity, but age-related thymic involution induces immune senescence 24 , which, combined with chronic comorbidities, elevates late-onset ADR risk. Second, omalizumab has broader clinical indications in adults, who frequently have comorbidities such as hypertension and diabetes; polypharmacy further increases ADR complexity. In children patients, omalizumab use is largely limited to core indications such as asthma, with simpler medication regimens, reducing confounding factors for ADR occurrence. This study has several inherent limitations that warrant consideration. First, the FAERS database is dominated by U.S. reports (>64%), with insufficient data from non-Western populations, which may limit the generalizability of the findings. Second, spontaneous reporting systems have inherent biases, including missing data and variable report quality between consumer and healthcare professional submissions, which may affect the accuracy of ADR signal detection. Third, disproportionality analysis only identifies an association between omalizumab and ADRs, not a causal relationship; further validation via prospective clinical trials is therefore required to confirm these findings. Conclusion Based on real-world data from the U.S. FAERS database, this study applied four disproportionality analysis methods to investigate post-marketing ADRs of omalizumab in children and adult populations. We identified marked age-specific differences in omalizumab’s ADR profiles, signal intensities, and onset timelines across the two groups. Clinically, precise, age-tailored monitoring protocols are warranted to maximize the clinical benefits of omalizumab therapy while minimizing associated safety risks. This study provides robust real-world evidence for the safe clinical use of omalizumab and offers a methodological reference for age-stratified pharmacovigilance research on biological agents. Reference 1. Pelaia C, Calabrese C, Terracciano R, Blasio F de, Vatrella A, Pelaia G. Omalizumab, the first available antibody for biological treatment of severe asthma: more than a decade of real-life effectiveness. Ther Adv Respir Dis 2018;12:1753466618810192. 2. Humbert M, Bousquet J, Bachert C, et al. IgE-Mediated Multimorbidities in Allergic Asthma and the Potential for Omalizumab Therapy. J Allergy Clin Immunol Pract 2019;7(5):1418–1429. 3. Chow TG, Franzblau LE, Khan DA. Adverse Reactions to Biologic Medications Used in Allergy and Immunology Diseases. Curr Allergy Asthma Rep 2022;22(12):195–207. 4. Agache I, Rocha C, Beltran J, et al. Efficacy and safety of treatment with biologicals (benralizumab, dupilumab and omalizumab) for severe allergic asthma: A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma. Allergy 2020;75(5):1043–1057. 5. Gon Y, Maruoka S, Mizumura K. Omalizumab and IgE in the Control of Severe Allergic Asthma. Front Pharmacol 2022;13:839011. 6. Maurer M, Kaplan A, Rosén K, et al. The XTEND-CIU study: Long-term use of omalizumab in chronic idiopathic urticaria. J Allergy Clin Immunol 2018;141(3):1138-1139.e7. 7. Kariyawasam HH, James LK. Chronic Rhinosinusitis with Nasal Polyps: Targeting IgE with Anti-IgE Omalizumab Therapy. Drug Des Devel Ther 2020;14:5483–5494. 8. Zhang Y, Liang B, Tian L, Chen B, Wu S. Systematic review and meta-analysis of omalizumab for IgE-mediated food allergy in children and young adults. Front Immunol 2025;16:1690650. 9. Ma T, Wang H, Wang X. Effectiveness and Response Predictors of Omalizumab in Treating Patients with Seasonal Allergic Rhinitis: A Real-World Study. J Asthma Allergy 2021;14:59–66. 10. Chan S, Cornelius V, Cro S, Harper JI, Lack G. Treatment Effect of Omalizumab on Severe Pediatric Atopic Dermatitis: The ADAPT Randomized Clinical Trial. JAMA Pediatr 2020;174(1):29–37. 11. Pongdee T, Li JT. Omalizumab safety concerns. J Allergy Clin Immunol 2025;155(1):31–35. 12. Elzagallaai AA, Greff M, Rieder MJ. Adverse Drug Reactions in Children: The Double-Edged Sword of Therapeutics. Clin Pharmacol Ther 2017;101(6):725–735. 13. Hanania NA, Alpan O, Hamilos DL, et al. Omalizumab in severe allergic asthma inadequately controlled with standard therapy: a randomized trial. Ann Intern Med 2011;154(9):573–582. 14. Deschildre A, Marguet C, Langlois C, et al. Real-life long-term omalizumab therapy in children with severe allergic asthma. Eur Respir J 2015;46(3):856–859. 15. Feng Z, Li X, Tong WK, et al. Real-world safety of PCSK9 inhibitors: A pharmacovigilance study based on spontaneous reports in FAERS. Front Pharmacol 2022;13:894685. 16. Shu Y, Wang L, Ding Y, Zhang Q. Disproportionality Analysis of Abemaciclib in the FDA Adverse Event Reporting System: A Real-World Post-Marketing Pharmacovigilance Assessment. Drug Saf 2023;46(9):881–895. 17. Caster O, Aoki Y, Gattepaille LM, Grundmark B. Disproportionality Analysis for Pharmacovigilance Signal Detection in Small Databases or Subsets: Recommendations for Limiting False-Positive Associations. Drug Saf 2020;43(5):479–487. 18. Montastruc J-L, Sommet A, Bagheri H, Lapeyre-Mestre M. Benefits and strengths of the disproportionality analysis for identification of adverse drug reactions in a pharmacovigilance database. Br J Clin Pharmacol 2011;72(6):905–908. 19. Luo L, Wang Y, Fu Y, Chen X, Liu S, Zhao B. Comprehensive safety assessment of ribociclib: A real-world analysis using the FDA Adverse Event Reporting System (FAERS) database. Br J Clin Pharmacol 2026;92(1):291–299. 20. Ciprandi G, Gallo F. The impact of gender on asthma in the daily clinical practice. Postgrad Med 2018;130(2):271–273. 21. Sirufo MM, De Pietro F, Ginaldi L, De Martinis M. Sex, Allergic Diseases and Omalizumab. Biomedicines 2022;10(2):328. 22. Carr EJ, Dooley J, Garcia-Perez JE, et al. The cellular composition of the human immune system is shaped by age and cohabitation. Nat Immunol 2016;17(4):461–468. 23. Song Y, Wang Z, Wang N, Xie X, Zhu T, Wang Y. A real-world pharmacovigilance study of omalizumab using disproportionality analysis in the FDA adverse drug events reporting system database. Sci Rep 2025;15:8045. 24. Palmer DB. The effect of age on thymic function. Front Immunol 2013;4:316. Conflict of Interest The authors declare no competing interests in relation to this research, authorship and publication of this manuscript. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Acknowledgements The authors acknowledge the U.S. FAERS database used in this study. Information & Authors Information Version history V1 Version 1 05 March 2026 Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations Hairui Zheng 0009-0007-1470-2256 Guangzhou First People's Hospital View all articles by this author Lu Liang Guangzhou First People's Hospital View all articles by this author Ning Li Guangzhou First People's Hospital View all articles by this author Yi Su [email protected] Guangzhou First People's Hospital View all articles by this author Metrics & Citations Metrics Article Usage 116 views 59 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Hairui Zheng, Lu Liang, Ning Li, et al. Age-Specific Differences in Omalizumab-Related Adverse Drug Reaction Signals between Children and Adults: An Analysis Based on the FAERS Database. Authorea . 05 March 2026. DOI: https://doi.org/10.22541/au.177270317.73494041/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. 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