Skip to main content
NCBI home page
Journal of Veterinary Internal Medicine logoLink to Journal of Veterinary Internal Medicine
. 2026 Feb 11;40(1):aalag003. doi: 10.1093/jvimsj/aalag003

Safety assessment of frunevetmab for osteoarthritis pain in cats: disproportionality analysis of the Food and Drug Administration Animal Drug Adverse Events database

Xiaoheng Lai 1,#, Li Lin 2,#, Yan Chen 3, Lifang Wu 4, Yaping Huang 5,✉, Maohua Chen 6,✉
PMCID: PMC12893208  PMID: 41742572

Abstract

Background

Frunevetmab is a felinized anti-nerve growth factor monoclonal antibody that alleviates osteoarthritis (OA) pain in cats by blocking nerve growth factor (NGF) signaling. While its efficacy is established, comprehensive real-world safety profiles remain limited.

Hypothesis/Objectives

To analyze frunevetmab-associated adverse events (AEs) using real-world data from the United States Food and Drug Administration (FDA) Animal Drug Adverse Events (ADAE) database.

Animals

Adverse event reports submitted for cats receiving frunevetmab, extracted from the FDA ADAE database (January 2022 - December 2024).

Methods

Disproportionality in frunevetmab-associated AEs was assessed by calculating the reporting odds ratio, the proportional reporting ratio, the Bayesian confidence-propagation neural network, and the multi-item gamma Poisson shrinker.

Results

From 33,378 feline AE reports, 5,248 frunevetmab-specific reports were analyzed. Frunevetmab-induced AEs spanned 24 system organ categories. Among the 19 significant preferred terms (PTs) identified, the most frequently reported AEs included pruritus, unspecified skin disorders, alopecia, dermatitis and eczema, and unspecified skin lesions. Notably, the AEs with the highest signal strength were skin ulceration, unspecified skin disorders, unspecified skin lesions, injection site pain, and dermatitis and eczema. In addition, unexpected significant AEs (e.g., abnormal cytology, arthritis, paresis) were detected, all of which were absent from the package insert.

Conclusions and clinical importance

We identified new potential AE signals for frunevetmab, emphasizing the need for robust clinical monitoring. Although these hypothesis-generating findings from disproportionality analysis require validation, they offer immediate, valuable guidance for veterinarians to optimize the safe use of this treatment in cats with OA.

Keywords: Frunevetmab, ADAE, adverse event, pharmacovigilance

Introduction

Osteoarthritis (OA) is a whole-joint degenerative disorder involving bone, cartilage, and synovium. It is the leading cause of chronic pain in cats, impacting > 25% of the feline population and resulting in impaired joint function, decreased mobility, and diminished quality of life.1-3 Given the risks of tolerance, dependence, and adverse effects, alongside regulatory hurdles, unpredictable pharmacology, and a lack of long-term safety data, the long-term use of opioids PO should not be included in chronic pain management.4,5 Nonsteroidal anti-inflammatory drugs (NSAIDs) form the cornerstone of pain management in cats.6,7 However, their long-term use for musculoskeletal disorders poses challenges and requires careful veterinary oversight. Nevertheless, regional labeling restrictions (eg, those in the United States [US] for meloxicam and robenacoxib, which limit administration to short-term) do not necessarily reflect the full scope of safe use. In other countries, labels support prolonged use, and studies confirm that longer-term treatment can be safe with appropriate patient selection, dosing, and monitoring.8 Notably, several established contraindications exist for administering NSAIDs to cats. Absolute contraindications include dehydration, hypotension, advanced (International Renal Interest Society [IRIS] stage 4) or progressive kidney disease, liver dysfunction (eg, hepatic lipidosis), concurrent treatment with nephrotoxic drugs (eg, aminoglycosides) or corticosteroids, and clinical signs of active gastrointestinal disease (eg, anorexia, vomiting).9 Currently, few drugs are available for cats suffering from chronic pain caused by OA. Overall, effective treatment options for managing OA pain in cats are limited.

Monoclonal antibodies (mAbs) targeting nerve growth factor (anti-NGF) have substantial potential for managing OA pain effectively.10 Frunevetmab is a felinized anti-NGF mAb that alleviates OA pain in cats by blocking NGF signaling.3,11,12 Frunevetmab is the sole anti-NGF mAb approved for cats in the US, the United Kingdom, and the European Union. Accordingly, it is recommended as a primary treatment for OA pain in cats according to World Small Animal Veterinary Association and American Animal Hospital Association guidelines.7,13

Nerve growth factor is secreted by Schwann cells in injured nerves and inflammatory cells in damaged tissues, and is vital for nociceptor sensitization in both acute and chronic pain conditions, such as OA. The interaction between NGF and the tropomyosin receptor kinase A (TrkA) receptor plays a crucial role in nociception and pain-related neural plasticity.14 Nerve growth factor activates a signaling cascade by binding to both TrkA and the p75 neurotrophin receptor (p75), thereby triggering neurite outgrowth and sensitization in neurons. Consequently, NGF induces peripheral and central sensitization. Analgesics that block NGF/TrkA signal transduction may exhibit high efficacy in these disorders.15

Research on the safety of anti-NGF mAbs in cats is lacking. The clinical development of anti-NGF mAbs for humans was set back in 2010 when the US Food and Drug Administration (FDA) temporarily suspended their clinical use because of joint toxicity and risks to the sympathetic nervous system. Although trials of tanezumab in humans resumed after the suspension was lifted in 2015, clinical trials in humans generally operate under strict inclusion criteria and for limited durations, which can obscure the full safety profile. Therefore, given the widespread use of the veterinary-specific anti-NGF mAb frunevetmab for cats with OA, diligent real-world safety monitoring in cats is paramount. The frunevetmab package insert lists vomiting, injection site pain, diarrhea, behavioral disorders, renal insufficiency, anorexia, lethargy, dermatitis, alopecia, dehydration, lameness, pruritus, weight loss, scabbing on the head or neck, gingival disorders, and bacterial skin infection as common adverse reactions.16 In addition, frunevetmab labeling includes a special note regarding neurologic adverse effects.16 Primates receiving higher doses of anti-NGF mAbs exhibited a decrease in the volume of postganglionic neuronal cell bodies. After discontinuation of the anti-NGF mAbs, the changes in cell body volume returned to normal. The US FDA has alerted veterinarians to post-marketing safety signals for bedinvetmab (Librela) in dogs. These signals have identified adverse neurologic events, including ataxia, seizures, paresis, and recumbency.17 Nerve growth factor plays a crucial role in the development of sensory and sympathetic nerve fibers in animals. This consideration is particularly pertinent when evaluating the use of frunevetmab in young, developing cats. The frunevetmab label explicitly states that the drug should not be used in breeding cats or in pregnant or lactating queens, because it may pass through the placental barrier and be excreted in milk. These warnings are supported by the observation of fetal abnormalities, increased rates of stillbirth, and increased postpartum mortality noted in rodents and primates receiving anti-NGF mAbs.16

The FDA’s Center for Veterinary Medicine maintains the Animal Drug Adverse Events (ADAE) database, an important public health resource that compiles reports of adverse events (AEs) and product defects associated with animal drugs and devices. The public can access this platform electronically. It is a critical pharmacovigilance system for monitoring the safety of veterinary drugs, devices, and animal food additives in the US. Currently, limited safety research and few reports are available on frunevetmab. We analyzed these AEs using real-world data from the ADAE database. Beyond corroborating extant safety information, this analysis identified novel potential hazards. These insights contribute to an expanded and refined data foundation, informing both clinical practice and public health policy formulation.

Methods

Study design and data source

The disproportionality analysis conducted for our study was structured as a case/non-case investigation aimed at quantifying the association between frunevetmab and AEs. The ratio of target AEs associated with frunevetmab (ie, cases) was compared to the ratio of AEs associated with all other pharmaceutical agents (ie, non-cases). A significant safety signal arises when frunevetmab demonstrates an increased likelihood of triggering target AEs compared with all other medications.

Our retrospective, observational pharmacovigilance study utilized animal and veterinary AE reports sourced from the FDA’s ADAE database (accessible at https://open.fda.gov/apis/animalandveterinary/event/download/),18 which is updated quarterly. Our study was conducted in accordance with the reporting of a disproportionality analysis for drug safety signal detection using individual case safety reports in pharmacovigilance (READUS-PV) guidelines to ensure transparent and standardized reporting.19 All reports analyzed in our study originated exclusively from the US. Cat AE reports linked to frunevetmab, submitted from the first quarter of 2022 to the fourth quarter of 2024, were retrieved from the ADAE database for the study.

Data extraction and analysis

We focused exclusively on “Solensia” and “FRUNEVETMAB” as the primary suspected drugs to maintain research specificity and accuracy. Data manipulation was efficiently performed using Python 3.10 (Python Software Foundation, Beaverton, OR, US) and Microsoft Excel 2019, facilitating thorough data processing. Throughout the screening process, no duplicate reports were identified. The Veterinary Dictionary for Drug-Related Affairs (VeDDRA) was utilized to acquire the system organ class (SOC) and preferred terms (PTs).20,21 The VeDDRA system is structured hierarchically in 4 levels: SOC at the apex, followed by high-level terms, PTs, and low-level terms at the base.

Descriptive analyses were performed to detail the clinical characteristics in frunevetmab-related reports. Where data allowed, comprehensive details were provided, including animal characteristics (age and weight), outcomes, reports, and year of reporting. The details are represented in Figure 1.

Figure 1.

Figure 1

Open in a new tab

The flow diagram of selecting frunevetmab-related AEs from the ADAE database. Abbreviations: ADAE = animal drug adverse events; AEs = adverse events.

The study employed several statistical analysis methods to evaluate the association between frunevetmab and potential AEs. The calculation methods, beginning with a descriptive statistical analysis of frunevetmab-related AE data, are detailed in Tables S1 and S2. Utilizing disproportionality and Bayesian analyses, we applied reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence–propagation neural network, and multi-item gamma Poisson shrinker to examine the associations between the drug and specified AEs. The AEs were considered signals when all 4 algorithms simultaneously satisfied the specified criteria.

Time to onset and duration

The onset time was determined by calculating the interval between the drug first-exposure date and the onset date. The duration of the event was determined using the duration value after standardization of its time unit.

Results

Descriptive analysis

We extracted all reported cases in cats from the ADAE database between the first quarter of 2022 and the fourth quarter of 2024, equaling 33 378 cases. After duplicates were deleted and screening was carried out, 5248 reports of frunevetmab-related AEs were obtained. These data were subsequently analyzed, with the general characteristics of the associated AEs listed in Table 1. Among AE reports in cats, females accounted for 54.29% and males for 45.63%. In terms of age distribution, the majority of AEs (83.59%) were observed in cats > 10 years of age, whereas the 6- to 10-year age group accounted for 13.39%. All reports originated exclusively from the US. The outcome categories included: euthanasia (6.21%), unknown status (13.17%), recovery/normal status (13.15%), ongoing events (63.41%), death (4.00%), and recovery with sequelae (0.06%). More than half of the cases were submitted by veterinarians (53.70%). The median time to onset of AEs was 5 days (interquartile range [IQR], 0-21), with a median duration of 16 days (IQR, 3-61). Considering the years 2022-2024, the highest reported year was 2024 (47.18%).

Table 1.

Characteristics of reports associated with frunevetmab.

Characteristics Frunevetmab-induced AE reports (n = 5248)
Number of events Available number, n Case number, n Case proportion
(%)
Gender, n (%) 4854 – 92.49
Female – 2635 54.29
Male – 2215 45.63
Other – 4 0.08
Age (years), n (%) 4795 – 91.37
< 1 8 0.17
1 ≤ and ≤ 6 137 2.86
6< and ≤ 10 – 642 13.39
>10 – 4008 83.59
Median (IQR) – 14 (12-16) –
Weight (kg), n (%) 4516 – 86.05
<2.5 – 99 2.19
2.5 ≤ and ≤ 5 – 2240 49.60
>5 – 2177 48.21
Median (IQR) – 4.99 (4.03-6.03) –
Reported countries, n (%) 5248 – 100.0
US 5248 100.0
Outcomes, n (%) 5247 – 99.98
Euthanized – 326 6.21
Outcome unknown – 691 13.17
Recovered/normal – 690 13.15
Ongoing – 3327 63.41
Died – 210 4.00
Recovered with sequela – 3 0.06
Time to onset (days) 5181 – 98.72
Median (IQR) – 5 (0-21) –
Duration of AE (days) 947 – 18.04
Median (IQR) – 16(3-61) –
Reporters, n (%) 5248 – 100.00
Veterinarian – 2818 53.70
Animal owner – 529 10.08
Other healthcare professional – 1823 34.74
Other – 78 1.49
Reporting year, n (%) 5248 – 100.00
2022 – 320 6.10
2023 – 2452 46.72
2024 – 2476 47.18
Open in a new tab

Abbreviations: AE, adverse event; US, United States.

Disproportionality analysis

Table 2 lists the 19 PTs that were found to be significantly disproportionate and that complied with all 4 algorithms. The most frequently reported frunevetmab-related AEs in terms of number of cases were pruritus (n = 1196), skin disorders not otherwise specified (NOS; n = 731), alopecia (n = 580), dermatitis and eczema (n = 492), and skin lesions NOS (n = 226). The 4 algorithms produced highly consistent screening results, with the most signals detected in skin and appendages disorders. The primary conditions included pruritus, unspecified skin disorders, alopecia, dermatitis and eczema, unspecified skin lesions, bacterial skin infections, erythema, and skin ulceration. The highest-ranking 5 PTs in terms of significance were skin ulceration (ROR 14.67), skin disorders NOS (ROR 14.47), skin lesion NOS (ROR 13.71), injection site pain (ROR 12.57), and dermatitis and eczema (ROR 12.51). Several significant AEs not listed on the drug label were identified, including abnormal cytology (n = 71; ROR 6.95, PRR 6.92, information component [IC] 1.80, empirical Bayesian geometric mean [EBGM] 3.48), arthritis (n = 43; ROR 8.57, PRR 8.55, IC 1.92, EBGM 3.78), paresis (n = 78; ROR 6.95, PRR 6.93, IC 1.80, EBGM 3.48), proprioception abnormality (n = 49; ROR 5.20, PRR 5.18, IC 1.61, EBGM 3.05), erythema (n = 127; ROR 4.12, PRR 4.10, IC 1.43, EBGM 2.70), skin ulceration (n = 91; ROR 14.67, PRR 14.60, IC 2.16, EBGM 4.45), and trauma NOS (n = 101; ROR 4.63, PRR 4.61, IC 1.52, EBGM 2.87).

Table 2.

Signal strength of reports associated with frunevetmab at the PT level.

SOC PTs Frunevetmab cases reporting PT ROR (95% 2-sided CI) PRR (χ 2 ) IC (IC025) EBGM (EBGM05)
Application site disorders Injection site pain 133 12.57 (9.14-17.29) 12.48 (400.87) 2.09 (1.52) 4.27 (3.10)
Application site disorders Injection site alopecia 60 8.09 (5.37-12.19) 8.06 (141.74) 1.89 (1.25) 3.69 (2.45)
Application site disorders Injection site lesion 47 7.32 (4.67-11.48) 7.30 (103.65) 1.83 (1.17) 3.55 (2.27)
Application site disorders Injection site pruritus 32 12.26 (6.43-23.37) 12.24 (95.46) 2.09 (1.09) 4.25 (2.23)
Ear and labyrinth disorders Ear pruritus 42 7.22 (4.49-11.59) 7.20 (91.67) 1.82 (1.13) 3.53 (2.20)
Investigations Abnormal cytologya 71 6.95 (4.85-9.96) 6.92 (150.56) 1.80 (1.25) 3.48 (2.42)
Musculoskeletal disorders Lameness 130 3.72 (2.96-4.66) 3.69 (146.98) 1.35 (1.07) 2.55 (2.03)
Musculoskeletal disorders Arthritisa 43 8.57 (5.23-14.04) 8.55 (105.50) 1.92 (1.17) 3.78 (2.31)
Neurological disorders Paresisa 78 6.95 (4.93-9.81) 6.93 (165.49) 1.80 (1.27) 3.48 (2.47)
Neurological disorders Proprioception abnormalitya 49 5.20 (3.48-7.76) 5.18 (81.09) 1.61 (1.08) 3.05 (2.04)
Skin and appendages disorders Pruritus 1196 4.66 (4.31-5.05) 4.40 (1710.65) 1.49 (1.37) 2.80 (2.59)
Skin and appendages disorders Skin disorders NOS 731 14.47 (12.55-16.68) 13.87 (2327.32) 2.14 (1.85) 4.40 (3.81)
Skin and appendages disorders Alopecia 580 5.64 (5.00-6.35) 5.47 (1020.68) 1.65 (1.46) 3.13 (2.78)
Skin and appendages disorders Dermatitis and eczema 492 12.51 (10.61-14.76) 12.17 (1473.48) 2.08 (1.77) 4.24 (3.60)
Skin and appendages disorders Skin lesion NOS 226 13.71 (10.66-17.65) 13.54 (707.17) 2.13 (1.65) 4.37 (3.39)
Skin and appendages disorders Bacterial skin infection 137 10.40 (7.75-13.96) 10.32 (375.73) 2.01 (1.50) 4.03 (3.00)
Skin and appendages disorders Erythemaa 127 4.12 (3.26-5.22) 4.10 (163.64) 1.43 (1.13) 2.70 (2.13)
Skin and appendages disorders Skin ulcerationa 91 14.67 (9.76-22.06) 14.60 (293.20) 2.16 (1.43) 4.45 (2.96)
Systemic disorders Trauma NOSa 101 4.63 (3.53-6.07) 4.61 (148.38) 1.52 (1.16) 2.87 (2.19)
Open in a new tab

Abbreviations: EBGM, empirical Bayesian geometric mean; EBGM05, the lower limit of 95% CI of EBGM; IC, information component; IC025, the lower limit of 95% CI of the IC; NOS, not otherwise specified; PRR, proportional reporting ratio; PTs, preferred terms; ROR, reporting odds ratio; SOC, system organ class; χ2, chi-square.

aIndicates a positive signal not described in the package insert.

Table 3 presents the SOC-level signal intensity of frunevetmab. As depicted in the figure data, frunevetmab-induced AEs targeted 24 organ systems. The significant SOCs meeting at least 1 of the 4 calculation criteria included skin and appendages disorders (n = 1888; ROR 5.06, PRR 4.31, IC 1.49, EBGM 2.81), neoplasia (n = 77; ROR 3.72, PRR 3.70, IC 1.37, EBGM 2.58), musculoskeletal disorders (n = 455; ROR 2.81, PRR 2.73, IC 1.09, EBGM 2.13), blood and lymphatic system disorders (n = 56; ROR 1.85, PRR 1.84, IC 0.70, EBGM 1.62), ear and labyrinth disorders (n = 14; ROR 1.82, PRR 1.81, IC 0.68, EBGM 1.60), renal and urinary disorders (n = 305; ROR 1.62, PRR 1.60, IC 0.55, EBGM 1.46), neurologic disorders (n = 861; ROR 1.09, PRR 1.08, IC 0.10, EBGM 1.07), metabolism and nutrition disorders (n = 4; ROR 1.04, PRR 1.04, IC 0.05, EBGM 1.03), immune system disorders (n = 82; ROR 1.02, PRR 1.02, IC 0.03, EBGM 1.02), and cardiovascular system disorders (n = 197; ROR 1.01, PRR 1.01, IC 0.01, EBGM 1.01).

Table 3.

Signal values of reports associated with frunevetmab at the SOC level.

SOC Frunevetmab cases reporting SOC ROR (95% 2-sided CI) PRR (χ 2 ) IC (IC025) EBGM (EBGM05)
Skin and appendages disorders 1888 5.06 (4.74-5.40)a 4.31 (2804.71)a 1.49 (1.40)a 2.81 (2.63)a
Neoplasia 77 3.72 (2.78-4.99)a 3.70 (88.93)a 1.37 (1.02)a 2.58 (1.92)
Musculoskeletal disorders 455 2.81 (2.50-3.15)a 2.73 (332.91)a 1.09 (0.97)a 2.13 (1.90)
Blood and lymphatic system disorders 56 1.85 (1.36-2.50)a 1.84 (15.93) 0.70 (0.51)a 1.62 (1.19)
Ear and labyrinth disorders 145 1.82 (1.50-2.20)a 1.81 (39.03) 0.68 (0.56)a 1.60 (1.32)
Renal and urinary disorders 305 1.62 (1.43-1.85)a 1.60 (54.22) 0.55 (0.48)a 1.46 (1.28)
Neurological disorders 861 1.09 (1.01-1.18)a 1.08 (5.06) 0.10 (0.09)a 1.07 (0.99)
Metabolism and nutrition disorders 4 1.04 (0.35-3.04) 1.04 (0.00) 0.05 (0.02)a 1.03 (0.35)
Immune system disorders 82 1.02 (0.81-1.30) 1.02 (0.03) 0.03 (0.02)a 1.02 (0.80)
Cardiovascular system disorders 197 1.01 (0.87-1.18) 1.01 (0.02) 0.01 (0.01)a 1.01 (0.87)
Eye disorders 139 0.92 (0.77-1.10) 0.92 (0.82) −0.10 (−0.12) 0.93 (0.78)
Investigations 846 0.90 (0.84-0.97) 0.91 (6.95) −0.11 (−0.12) 0.92 (0.86)
Digestive tract disorders 1166 0.85 (0.79-0.91) 0.87 (24.17) −0.18 (−0.19) 0.88 (0.83)
Behavioral disorders 798 0.78 (0.72-0.84) 0.79 (41.42) −0.29 (−0.31) 0.82 (0.76)
Hepato-biliary disorders 26 0.76 (0.50-1.15) 0.76 (1.68) −0.33 (−0.50) 0.79 (0.53)
Medication and product use errors 106 0.74 (0.60-0.91) 0.74 (8.44) −0.37 (−0.45) 0.77 (0.63)
Systemic disorders 2428 0.70 (0.67-0.74) 0.77 (200.06) −0.32 (−0.33) 0.80 (0.76)
Respiratory tract disorders 257 0.59 (0.52-0.67) 0.60 (64.61) −0.64 (−0.73) 0.64 (0.56)
Endocrine system disorders 67 0.52 (0.40-0.66) 0.52 (27.55) −0.83 (−1.07) 0.56 (0.44)
Product defects 1 0.47 (0.06-3.66) 0.47 (0.54) −0.95 (−7.39) 0.52 (0.07)
Application site disorders 293 0.33 (0.29-0.37) 0.35 (360.81) −1.36 (−1.53) 0.39 (0.35)
Reproductive system disorders 4 0.23 (0.09-0.63) 0.23 (9.65) −1.91 (−5.20) 0.27 (0.10)
Other event 4 0.18 (0.07-0.48) 0.18 (14.58) −2.28 (−6.17) 0.21 (0.08)
Mammary gland disorders 1 0.08 (0.01-0.54) 0.08 (11.21) −3.50 (−25.19) 0.09 (0.01)
Open in a new tab

Abbreviations: EBGM, empirical Bayesian geometric mean; EBGM05, the lower limit of 95% CI of EBGM; IC, information component; IC025, the lower limit of 95% CI of the IC; PRR, proportional reporting ratio; ROR, reporting odds ratio; SOC, system organ class; χ2, chi-square.

aIndicates statistically significant signals in the algorithm.

Time to onset and duration of AEs

The duration of dosing and time to onset of frunevetmab-related AEs were obtained from the database, with 5181 AE reports (98.72%) providing details. The median onset time was 5 days (IQR, 0-21 days). Most frunevetmab-related AEs occurred within the first month after initial treatment (n = 4369, 84.33%, Figure 2A), whereas approximately 7.43% (n = 385) and 2.24% (n = 116) of AEs occurred 2 and 3 months later, respectively. The majority (n = 571, 60.30%, Figure 2B) of frunevetmab-related AEs had a duration ≤ 1 month. The median duration of AEs was 16 days (IQR, 3-61 days).

Figure 2.

Figure 2

Open in a new tab

Time to onset and duration of frunevetmab-related adverse events. (A) Time to onset. (B) Duration.

Discussion

We assessed frunevetmab’s safety using extensive real-world pharmacovigilance data. We aimed to raise clinical awareness regarding drug-related AEs and provide a reference for the safe use of this medication.

Osteoarthritis is prevalent, especially among older cats. In a previous study, of 100 cats recruited consecutively for the study, 61% had OA in at least 1 joint; 48% exhibited OA in multiple joints. All of the cats were ≥ 6 years of age. Eighty-two percent of cats > 14 years exhibited OA in at least 1 joint.2 Osteoarthritis is common in cats, and its prevalence increases with age.22 The median age of cats with OA and other degenerative arthropathies was 10.2 years, suggesting that older age is an important risk factor.23 This observation is consistent with our finding that 83.59% of frunevetmab-related AEs were reported in cats > 10 years of age. Osteoarthritis occurs more frequently in women than in men.24 Our reported data identified a higher proportion of females (54.29%) among the frunevetmab-related AE reports. Our findings highlight the importance of closely monitoring AEs in geriatric female cats, particularly those > 10 years of age. Although deaths and euthanasia have occurred after frunevetmab administration, no causal relationship with the product has been established. In such cases, owners often decline necropsy, which makes it difficult to determine the cause of death.

In our study, the largest signal count corresponded to skin and appendage disorders, which included pruritus, skin disorders NOS, alopecia, dermatitis and eczema, skin lesion NOS, bacterial skin infection, erythema, and skin ulceration. This category also had higher case reports (n = 1888) and stronger signal scores (ROR 5.06, PRR 4.31, IC 1.49, EBGM 2.81) than other AE categories. A case series investigating skin AEs in 5 cats after SC frunevetmab injection indicated that all exhibited moderate to severe pruritus, resulting in self-inflicted trauma to the neck, head, or both.25 This occurrence resulted in lesions that varied from superficial dermatitis to alopecia and ulceration. In case 1, corticosteroids alleviated pruritus, but surgical resection was required to eliminate the skin lesion. In cases 2-5, clinical signs subsided within 2-6 weeks after the last dose of frunevetmab. A randomized controlled trial determined that frunevetmab-treated cats exhibited higher frequencies of AEs such as alopecia, dermatitis and eczema, pruritus, unspecified skin disorders, unspecified skin lesions, and bacterial skin infections compared with those receiving a placebo.11 Among the cats treated with frunevetmab, 6.0% (11/182) experienced dermatitis and eczema, 5.5% (10/182) developed alopecia, and 3.8% (7/182) had pruritus.11 Of the 32 cats with dermatologic conditions receiving frunevetmab, 13 did not require therapeutic intervention. However, skin conditions failed to improve in 3 frunevetmab-treated cats: 2 presented with skin masses and 1 with alopecia. Some studies suggest that these AEs may be associated with the wearing of activity-monitoring collars.12 Although the package insert mentions skin and appendage disorders, our data provide a detailed breakdown of the numbers of cases and values of signals for skin AEs related to frunevetmab, offering clinicians crucial information to help them quickly identify this AE.

Frunevetmab had significant pharmacovigilance signals for renal and urinary disorders (n = 305; ROR 1.62, IC 0.55), with both case volume and signal strength exceeding background expectations. The approved product monograph for frunevetmab cites renal impairment as an AE observed during clinical development and post-marketing surveillance.12,26 A previous study conducted renal biopsies on 24 human patients (11 females and 13 males, aged 12-78 years) with various kidney diseases.27 The results demonstrated the presence of NGF and TrkA in renal tubular and glomerular cells, and p75-immunopositivity in interstitial and mesangial cells. The study identified TrkA-NGF co-localization but an absence of TrkA-p75 co-localization in tubular and glomerular cells. This pattern suggests that NGF synthesis and utilization may be autocrine-regulated. The results suggest that NGF signaling is crucial in renal and glomerular injury responses in humans. In a placebo-controlled, pilot, blinded clinical study, 3 cats developed serum creatinine concentrations above the reference range (increased from baseline).28 One serious AE was reported in a cat receiving 0.4 mg/kg of NV-02, a felinized anti-NGF mAb, but it was deemed to be unrelated to the treatment. Initially, this cat was classified with IRIS stage 2 chronic kidney disease (CKD). On day 77, the owner reported progressive behavioral changes (increased hiding) and decreased appetite over the preceding 10 days. The cat lost 0.72 kg (16.5% weight loss from baseline) and exhibited azotemia, hyperglobulinemia, and leukocytosis with a left shift on day 77 laboratory assessment. Euthanasia was elected over supportive treatment. Up to 70% of older cats with painful OA have concurrent CKD.29 Published data on the safety and efficacy of frunevetmab for cats with both OA and CKD are currently limited. We advise veterinarians to maintain awareness of these potential AEs and implement ongoing renal function monitoring during frunevetmab treatment, particularly in geriatric cats with concomitant renal impairment.

Our real-world data identified important pharmacovigilance signals for paresis (n = 78; ROR 6.95, PRR 6.93, IC 1.80, EBGM 3.48) and proprioceptive abnormalities (n = 49; ROR 5.20, PRR 5.18, IC 1.61, EBGM 3.05), with statistical significance in disproportionality analyses. Exposure to NGF antibodies over a prolonged period caused significant atrophy of the cell bodies of the superior cervical ganglion in rodent models, resulting in the loss of adrenergic nerve terminals in various peripheral tissues.30-32 Primates subjected to extended high doses of anti-NGF mAbs showed a decrease in postganglionic sympathetic cell body size, which reversed after stopping treatment.33 Reversible decrease in superior cervical ganglion volume and neuronal size similarly were observed in the Sprague-Dawley rats after administration of anti-NGF mAbs.34

Clinical trials in humans have shown that patients receiving anti-NGF mAb treatment experience rapidly progressive OA, with a dose-dependent relationship.35 The cause of worsening OA in some individuals is not fully understood. From 2010 to 2012, the FDA temporarily suspended development programs for the use of anti-NGF mAbs in humans because of an increase in serious joint-related AEs.36 This condition was observed more frequently in human patients receiving long-term (>90 days) concomitant NSAIDs and anti-NGF mAbs.14 As of yet, no safety data are available on the concurrent use of NSAIDs and frunevetmab in cats. Bedinvetmab, another approved treatment for OA in dogs, showed a notably higher occurrence of severe musculoskeletal AEs in treated dogs, such as ligament and tendon injuries, polyarthritis, fractures, musculoskeletal tumors, and septic arthritis.37,38 These findings are consistent with previous FDA pharmacovigilance concerns about musculoskeletal and neurologic AEs associated with bedinvetmab administration.39 Our research found that frunevetmab was linked to AEs such as arthritis and lameness, aligning with findings from earlier clinical trials. However, it remains undetermined whether lameness observed in cats during frunevetmab treatment arises from the progression of underlying arthritis or represents a drug-induced AE.

A randomized, double-blind, placebo-controlled trial assessed the efficacy of monthly frunevetmab. A total of 275 cats were enrolled (frunevetmab: n = 182; placebo: n = 93), all of which received at least 1 treatment dose. Gastrointestinal disorders, such as vomiting and diarrhea, were the most common AEs, occurring at similar rates in both the placebo group (19/93, 20.43%) and the frunevetmab group (45/182, 24.73%).11 Although the product label suggests a potential association with activity-monitoring collars,16 a direct causal link with gastrointestinal signs is unlikely. A more plausible explanation is that the collars acted as a stressor, potentially inducing vomiting in individuals susceptible to stress. The comparable incidence between groups, together with the absence of a significant signal in our disproportionality analysis, suggests that, although these gastrointestinal events are documented in the label, they do not appear to be directly attributable to the drug in this specific context.

Bedinvetmab is another anti-NGF mAb approved for managing OA pain, specifically in dogs. Despite having the same anti-NGF mechanism for managing OA pain, frunevetmab (feline) and bedinvetmab (canine) have divergent, species-specific AE profiles.40 The profile for cats is dominated by dermatologic events (eg, pruritus, alopecia, and skin ulceration), whereas the profile for dogs is characterized by neurologic (eg, ataxia) and urinary (eg, incontinence, polyuria) signs, alongside gastrointestinal events such as anorexia and vomiting. Musculoskeletal AEs also differ markedly. Bedinvetmab in dogs has been associated with severe traumatic injuries (eg, tendon or ligament damage, fractures),37,38 whereas frunevetmab in cats has been linked to lameness, arthritis, and neuromuscular events (eg, paresis). Regarding urinary disorders, bedinvetmab typically causes reversible signs such as polyuria, whereas frunevetmab is associated with a broader signal of renal and urinary disorders. Consequently, clinical monitoring must be species-specific. For frunevetmab in cats, the focus should be on dermatologic, urinary, neuromuscular, and articular events. For bedinvetmab in dogs, neurologic, urinary, musculoskeletal, and gastrointestinal systems should be monitored.

Our study had several limitations that are inherent to the use of a voluntarily reported AE database. Firstly, the data source is fundamentally constrained by the lack of a true exposure denominator, which precludes the calculation of incidence rates and limits the assessment of absolute risk. In addition, the database relies exclusively on US data, which may restrict its generalizability globally.41 Secondly, spontaneous reporting systems are subject to under-reporting (Weber effect), and various reporting biases, including notoriety bias, reporter bias, and potential misclassification when reports originate from pet owners.41-44 Thirdly, with regard to causal inference, the detection of a safety signal indicates a statistical association, but does not prove causation. Many reported AEs may be related to underlying conditions, comorbidities, or concomitant medications. Confounding by indication is another inherent challenge.41 Finally, limitations in data quality include the absence of AE severity grading, incomplete information, unadjusted confounders, and a lack of standardized terminology, which may lead to conditions such as arthritis being misclassified as an underlying disease rather than a potential AE.44 These limitations collectively emphasize the exploratory nature of signal detection and highlight the need for confirmatory studies.

Conclusion

We utilized the ADAE database to detect and analyze AE signals associated with frunevetmab in real-world settings. The emergence of unexpected AEs, including arthritis, paresis, proprioception abnormalities, and skin ulceration necessitates a reassessment of frunevetmab’s safety profile, particularly its potential effects on the integumentary, neurologic, and musculoskeletal systems. Until prospective study evidence is available, the following clinical precautions are advised: (1) monitor joint function, renal function, skin integrity, and neurologic system; (2) report new-onset arthritis, skin ulceration, or worsening renal function to regulatory authorities; and (3) avoid use in animals with pre-existing neuromuscular disorders or renal insufficiency. Our study provides valuable insight into frunevetmab’s safety profile and should help veterinarians make informed clinical decisions when selecting treatments for OA.

Supplementary Material

aalag003_supplemental_table
aalag003_supplemental_table.docx (25.7KB, docx)

Abbreviations

ADAE

animal drug adverse events

AE

adverse event

CKD

chronic kidney disease

EBGM

empirical Bayesian geometric mean

FDA

Food and Drug Administration

IC

information component

IRIS

International Renal Interest Society

mAbs

monoclonal antibodies

NGF

nerve growth factor

NOS

not otherwise specified

NSAIDs

nonsteroidal anti-inflammatory drugs

OA

osteoarthritis

PRR

proportional reporting ratio

PT

preferred term

READUS-PV

reporting of a disproportionality analysis for drug safety signal detection using individual case safety reports in pharmacovigilance

ROR

reporting odds ratio

SOC

system organ class

TrkA

tropomyosin receptor kinase A

US

United States

VeDDRA

Veterinary Dictionary for Drug-Related Affairs

Contributor Information

Xiaoheng Lai, Department of Pharmacy, Second Affiliated Hospital of Xiamen Medical College, No. 566 Shengguang Street, Xiamen, Fujian 361024, China.

Li Lin, Department of Medical Oncology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, No. 134 Dongjie Street, Fuzhou 350001, Fujian, China.

Yan Chen, Department of Pharmacy, Pingtan Comprehensive Experimental Area Hospital, Pingtan Comprehensive Experimental Area, Fuzhou, Fujian 350400, PR China.

Lifang Wu, Department of Pharmacy, Second Affiliated Hospital of Xiamen Medical College, No. 566 Shengguang Street, Xiamen, Fujian 361024, China.

Yaping Huang, Department of Pharmacy, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, No. 134 Dongjie Street, Fuzhou, Fujian 350001, PR China.

Maohua Chen, Department of Pharmacy, Pingtan Comprehensive Experimental Area Hospital, Pingtan Comprehensive Experimental Area, Fuzhou, Fujian 350400, PR China.

Author contributions

Xiaoheng Lai (Conceptualization, Validation, Writing—original draft, Writing—review & editing), Li Lin (Conceptualization, Validation, Writing—original draft, Writing—review & editing), Yan Chen (Validation, Writing—review & editing), Lifang Wu (Validation), Yaping Huang (Data curation, Formal analysis, Software, Supervision, Visualization), and Maohua Chen (Data curation, Formal analysis, Software, Supervision, Visualization)

Conflicts of interest

The authors have no conflicts of interest to report.

Funding

The authors declare no funding to report.

Off-label antimicrobial declaration

The authors declare no off-label use of antimicrobials.

Institutional animal care and use committee or other approval declaration

The authors declare no institutional animal care and use committee or other approval was needed.

Human ethics approval declaration

The authors declare human ethics approval was not needed.

References

  • 1. Lefort-Holguin  M, Delsart  A, Frézier  M, et al.  Osteoarthritis in cats: what we know, and mostly, what we don’t know. . . Yet. J Feline Med Surg. 2025;27:1098612x251347999. 10.1177/1098612X251347999 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. Slingerland  LI, Hazewinkel  HA, Meij  BP, Picavet  P, Voorhout  G. Cross-sectional study of the prevalence and clinical features of osteoarthritis in 100 cats. Vet J. 2011;187:304-309. 10.1016/j.tvjl.2009.12.014 [DOI] [PubMed] [Google Scholar]
  • 3. Reid  J, Gildea  E, Davies  V, Thompson  J, Scott  M. Measuring the effect of the anti-nerve growth factor antibodies bedinvetmab and frunevetmab on quality of life in dogs and cats with osteoarthritis using a validated health-related quality of life outcome measure: an observational real-world study. Front Vet Sci. 2024;11:1395360. 10.3389/fvets.2024.1395360 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4. Guedes  AGP, Meadows  JM, Pypendop  BH, Johnson  EG. Evaluation of tramadol for treatment of osteoarthritis in geriatric cats. J Am Vet Med Assoc. 2018;252:565-571. 10.2460/javma.252.5.565 [DOI] [PubMed] [Google Scholar]
  • 5. Monteiro  BP, Klinck  MP, Moreau  M, et al.  Analgesic efficacy of tramadol in cats with naturally occurring osteoarthritis. PLoS One. 2017;12:e0175565. 10.1371/journal.pone.0175565 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. Steagall  PV, Robertson  S, Simon  B, Warne  LN, Shilo-Benjamini  Y, Taylor  S. 2022 ISFM consensus guidelines on the management of acute pain in cats. J Feline Med Surg. 2022;24:4-30. 10.1177/1098612X211066268 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. Monteiro  BP, Lascelles  BDX, Murrell  J, Robertson  S, Steagall  PVM, Wright  B. 2022 WSAVA guidelines for the recognition, assessment and treatment of pain. J Small Anim Pract. 2023;64:177-254. 10.1111/jsap.13566 [DOI] [Google Scholar]
  • 8. Gunew  MN, Menrath  VH, Marshall  RD. Long-term safety, efficacy and palatability of oral meloxicam at 0.01-0.03 mg/kg for treatment of osteoarthritic pain in cats. J Feline Med Surg. 2008;10:235-241. 10.1016/j.jfms.2007.10.007 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. Taylor  S, Gruen  M, KuKanich  K, et al.  2024 ISFM and AAFP consensus guidelines on the long-term use of NSAIDs in cats. J Feline Med Surg. 2024;26:1098612x241241951. 10.1177/1098612X241241951 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. Bannwarth  B, Kostine  M. Targeting nerve growth factor (NGF) for pain management: what does the future hold for NGF antagonists?  Drugs. 2014;74:619-626. 10.1007/s40265-014-0208-6 [DOI] [PubMed] [Google Scholar]
  • 11. Gruen  ME, Myers  JAE, Tena  JS, Becskei  C, Cleaver  DM, Lascelles  BDX. Frunevetmab, a felinized anti-nerve growth factor monoclonal antibody, for the treatment of pain from osteoarthritis in cats. J Vet Intern Med. 2021;35:2752-2762. 10.1111/jvim.16291 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. Gruen  ME, Myers  JAE, Lascelles  BDX. Efficacy and safety of an anti-nerve growth factor antibody (frunevetmab) for the treatment of degenerative joint disease-associated chronic pain in cats: a multisite pilot field study. Front Vet Sci. 2021;8:610028. 10.3389/fvets.2021.610028 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. Gruen  ME, Lascelles  BDX, Colleran  E, et al.  2022 AAHA pain management guidelines for dogs and cats. J Am Anim Hosp Assoc. 2022;58:55-76. 10.5326/JAAHA-MS-7292 [DOI] [PubMed] [Google Scholar]
  • 14. Enomoto  M, Mantyh  PW, Murrell  J, Innes  JF, Lascelles  BDX. Anti-nerve growth factor monoclonal antibodies for the control of pain in dogs and cats. Vet Rec. 2019;184:23. 10.1136/vr.104590 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. Hirose  M, Kuroda  Y, Murata  E. NGF/TrkA Signaling as a therapeutic target for pain. Pain Pract. 2016;16:175-182. 10.1111/papr.12342 [DOI] [PubMed] [Google Scholar]
  • 16. U.S. Food and Drug Administration . FDA labelsPLUS: Solensia (frunevetmab injection) for cats. 2022. Accessed November 8, 2025. https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/a73b79c4-3623-4b52-81ea-6180528a031e/spl-doc?hl=frunevetmab
  • 17. U.S. Food and Drug Administration . FDA notifies veterinarians about adverse events reported in dogs treated with Librela (bedinvetmab injection). https://www.fda.gov/animal-veterinary/product-safety-information/dear-veterinarian-letter-notifying-veterinarians-about-adverse-events-reported-dogs-treated-librela
  • 18. U.S. Food and Drug Administration . Animal & Veterinary Adverse Events. Accessed August 1, 2025. https://open.fda.gov/apis/animalandveterinary/event/download/
  • 19. Fusaroli  M, Salvo  F, Begaud  B, et al.  The REporting of a disproportionality analysis for DrUg safety signal detection using individual case safety reports in Pharmaco vigilance (READUS-PV): explanation and elaboration. Drug Saf. 2024; 47:585-599. 10.1007/s40264-024-01423-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. European Medicines Agency CVMP . Combined Veddra List of Clinical Terms for Reporting Suspected Adverse Events in Animals and Humans to Veterinary Medicinal Products. European Medicines Agency; 2023. [Google Scholar]
  • 21. European Medicines Agency CVMP . Guidance Notes on the Use of Veddra Terminology for Reporting Suspected Adverse Events in Animals and Humans. European Medicines Agency; 2023. [Google Scholar]
  • 22. Bennett  D, SMbZ  A, Johnston  P. Osteoarthritis in the cat. J Feline Med Surg. 2012;14:65-75. 10.1177/1098612X11432828 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Clarke  SP, Mellor  D, Clements  DN, et al.  Prevalence of radiographic signs of degenerative joint disease in a hospital population of cats. Vet Rec. 2005;157:793-799. 10.1136/vr.157.25.793 [DOI] [PubMed] [Google Scholar]
  • 24. Cross  M, Smith  E, Hoy  D, et al.  The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014;73:1323-1330. 10.1136/annrheumdis-2013-204763 [DOI] [PubMed] [Google Scholar]
  • 25. Storrer  A, Mackie  JT, Gunew  MN, Aslan  J. Cutaneous lesions and clinical outcomes in five cats after frunevetmab injections. J Feline Med Surg. 2023;25:1098612x231198416. 10.1177/1098612X231198416 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. Richard  R, de  Camargo  MM, Bruyette  D. Use of solensia (frunevetmab) in nondomestic felids (Panthera tigris, Lynx rufus, Panthera uncia) guided by protein sequence analysis. J Zoo Wildl Med. 2024;55:780-787. 10.1638/2023-0122 [DOI] [PubMed] [Google Scholar]
  • 27. Bonofiglio  R, Antonucci  MT, Papalia  T, et al.  Nerve growth factor (NGF) and NGF-receptor expression in diseased human kidneys. J Nephrol. 2007;20:186-195. [PubMed] [Google Scholar]
  • 28. Gruen  ME, Thomson  AE, Griffith  EH, Paradise  H, Gearing  DP, Lascelles  BD. A feline-specific anti-nerve growth factor antibody improves mobility in cats with degenerative joint disease-associated pain: a pilot proof of concept study. J Vet Intern Med. 2016;30:1138-1148. 10.1111/jvim.13972 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29. Marino  CL, Lascelles  BD, Vaden  SL, Gruen  ME, Marks  SL. Prevalence and classification of chronic kidney disease in cats randomly selected from four age groups and in cats recruited for degenerative joint disease studies. J Feline Med Surg. 2014;16:465-472. 10.1177/1098612X13511446 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30. Gorin  PD, Johnson  EM  Jr. Effects of long-term nerve growth factor deprivation on the nervous system of the adult rat: an experimental autoimmune approach. Brain Res. 1980;198:27-42. 10.1016/0006-8993(80)90341-8 [DOI] [PubMed] [Google Scholar]
  • 31. Ruit  KG, Osborne  PA, Schmidt  RE, Johnson  EM  Jr, Snider  WD. Nerve growth factor regulates sympathetic ganglion cell morphology and survival in the adult mouse. J Neurosci. 1990;10:2412-2419. 10.1523/JNEUROSCI.10-07-02412.1990 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32. Bjerre  B, Wiklund  L, Edwards  DC. A study of the de- and regenerative changes in the sympathetic nervous system of the adult mouse after treatment with the antiserum to nerve growth factor. Brain Res. 1975;92:257-278. 10.1016/0006-8993(75)90274-7 [DOI] [PubMed] [Google Scholar]
  • 33. Belanger  P, Butler  P, Butt  M, et al.  From the cover: evaluation of the effects of tanezumab, a monoclonal antibody against nerve growth factor, on the sympathetic nervous system in adult Cynomolgus monkeys (Macaca fascicularis): a stereologic, histomorphologic, and cardiofunctional assessment. Toxicol Sci. 2017;158:319-333. 10.1093/toxsci/kfx089 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34. Kigami  D, Butt  MT, Brown  DL, Matsumoto  M, Ito  H. Neurotoxicity studies with a tropomyosin-related kinase a inhibitor, ASP7962, on the sympathetic and sensory nervous systems in rats. Toxicol Lett. 2021;344:34-45. 10.1016/j.toxlet.2021.02.018 [DOI] [PubMed] [Google Scholar]
  • 35. Hochberg  MC. Serious joint-related adverse events in randomized controlled trials of anti-nerve growth factor monoclonal antibodies. Osteoarthr Cartil. 2015;23:S18-S21. 10.1016/j.joca.2014.10.005 [DOI] [PubMed] [Google Scholar]
  • 36. McKelvey  L, Shorten  GD, O'Keeffe  GW. Nerve growth factor-mediated regulation of pain signalling and proposed new intervention strategies in clinical pain management. J Neurochem. 2013;124:276-289. 10.1111/jnc.12093 [DOI] [PubMed] [Google Scholar]
  • 37. Brunke  MW, Dewey  CW. Commentary: musculoskeletal adverse events in dogs receiving bedinvetmab (Librela). Front Vet Sci. 2025;12:2025. 10.3389/fvets.2025.1628681 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38. Farrell  M, Waibel  FWA, Carrera  I, et al.  Musculoskeletal adverse events in dogs receiving bedinvetmab (Librela). Front Vet Sci. 2025;12:1581490. 10.3389/fvets.2025.1581490 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39. U.S. Food and Drug Administration . FDA notifies veterinarians about adverse events reported in dogs treated with Librela (bedinvetmab injection). Accessed January 6, 2025. https://www.fda.gov/animal-veterinary/product-safety-information/dear-veterinarian-letter-notifying-veterinarians-about-adverse-events-reported-dogs-treated-librela
  • 40. Monteiro  BP, Simon  A, Knesl  O, et al.  Global pharmacovigilance reporting of the first monoclonal antibody for canine osteoarthritis: a case study with bedinvetmab (Librela™). Front Vet Sci. 2025;12:1558222. 10.3389/fvets.2025.1558222 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41. Noguchi  Y, Tachi  T, Teramachi  H. Detection algorithms and attentive points of safety signal using spontaneous reporting systems as a clinical data source. Brief Bioinform. 2021;22:1-14. 10.1093/bib/bbab347 [DOI] [PubMed] [Google Scholar]
  • 42. Matsuda  S, Aoki  K, Kawamata  T, et al.  Bias in spontaneous reporting of adverse drug reactions in Japan. PLoS One. 2015;10:e0126413. 10.1371/journal.pone.0126413 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43. Hazell  L, Shakir  SA. Under-reporting of adverse drug reactions: a systematic review. Drug Saf. 2006;29:385-396. 10.2165/00002018-200629050-00003 [DOI] [PubMed] [Google Scholar]
  • 44. Moulis  G, Sommet  A, Durrieu  G, et al.  Trends of reporting of “serious” vs. “non-serious” adverse drug reactions over time: a study in the French Pharmaco vigilance database. Br J Clin Pharmacol. 2012;74:201-204. 10.1111/j.1365-2125.2012.04185.x [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

aalag003_supplemental_table
aalag003_supplemental_table.docx (25.7KB, docx)

Articles from Journal of Veterinary Internal Medicine are provided here courtesy of Oxford University Press

RESOURCES