Bedinvetmab (Librela) Pharmacovigilance: Farrell Data vs Zoetis Rebuttal

TL;DR

A published commentary from Zoetis researchers challenges the methodology and conclusions of the Farrell et al. musculoskeletal adverse-event report for bedinvetmab (Librela), arguing that the disproportionality analysis is invalid due to incomplete reference datasets and that the case series lacks rigour for causal inference.

What just dropped

• Farrell et al. (Frontiers in Veterinary Science, 2025) reported an increased disproportionate reporting rate of musculoskeletal adverse events in dogs receiving bedinvetmab using data extracted from the EudraVigilance Veterinary (EVV) open-access database, and presented a case series of 19 dogs with suspected joint-related adverse events including features resembling rapidly progressive osteoarthritis. (https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2025.1581490/full)
• Werts et al. (Zoetis, Frontiers in Veterinary Science General Commentary, 2025) formally responded, arguing that the EVV data extracted by Farrell et al. are complete for bedinvetmab but significantly incomplete for every other product in the comparator set, because Zoetis reported up to three years of historical non-serious data to EVV during the regulatory transition in 2022 while other manufacturers' historical data are missing. Zoetis also identified methodological problems with the disproportionality approach and case adjudication. (https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2025.1663398/full)

Context

Bedinvetmab (Librela) is an anti-nerve growth factor (anti-NGF) monoclonal antibody approved for alleviation of pain associated with osteoarthritis in dogs. NGF inhibition has been associated with rapidly progressive osteoarthritis (RPOA) in humans, which prompted both the FDA and EMA to include precautionary label statements. The Farrell et al. paper attempted to quantify whether a similar signal exists in veterinary pharmacovigilance databases and described 19 clinical cases.

The Zoetis commentary identifies three core methodological problems with the Farrell et al. analysis. First, the EVV data for bedinvetmab is complete because Zoetis retrospectively uploaded up to three years of historical non-serious reports during the 2022 regulatory transition; this creates an asymmetry where bedinvetmab appears to have a disproportionate reporting rate compared to other products whose pre-2022 non-serious reports are absent from EVV. Second, the study does not use the established proportional reporting ratio (PRR) or reporting odds ratio (ROR) methods with confidence intervals; referring to the approach as disproportionality analysis does not align with the standard definition of that term. Third, the 19-case series used a subjective adjudication system without blinding to treatment status, lacked a true control arm, and did not account for pre-existing chronic NSAID use in 14 of 19 cases. Target animal safety studies for bedinvetmab using up to 10 times the recommended dose with extensive joint histopathology did not identify joint risk.

What this changes in Bedinvetmab (Librela) Adverse Events in Dogs (https://www.thevoyage.ai/forvets/knowledge/bedinvetmab-librela-adverse-events-dogs)

Clinicians who have been monitoring the Farrell et al. signal should be aware of the Zoetis rebuttal and the specific database asymmetry argument. The current state of the evidence does not permit a definitive conclusion on whether bedinvetmab causes a canine equivalent of human RPOA: the Farrell et al. data generate a hypothesis, but the methodology cannot support the causal conclusion drawn. The Werts et al. commentary does not dispute the possibility of any adverse event and notes that Zoetis continues to investigate reports. Veterinary professionals are encouraged to report suspected adverse drug reactions through national pharmacovigilance systems for any veterinary medicine. Individual patient benefit-risk assessment remains the appropriate framework for prescribing decisions.

Voyage Clinical Desk: https://www.thevoyage.ai/forvets/ask?context=bedinvetmab-librela-adverse-events-dogs

References

1. Farrell M et al. 2025. Musculoskeletal adverse events in dogs receiving bedinvetmab (Librela). Front Vet Sci 12:1581490. https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2025.1581490/full
2. Werts A et al. (Zoetis). 2025. Commentary: Musculoskeletal adverse events in dogs receiving bedinvetmab (Librela). Front Vet Sci 12:1663398. https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2025.1663398/full

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