Librela and Rapidly Progressing Arthritis.

Hello, Summarians!

Unintended consequences. Unexpected results. Unpredicted outcome. These phrases suggest that we had no idea of the potential side effects of a particular action or treatment. They are the perfect chicken/egg metaphor.

It begs the question — is that true? Sometimes it is the literal truth, and other times it may not be as clear.

One way we try to obtain clarity is by continuing research. Three different topics for you to explore. 🙂 

Pica and GI Disease in Dogs

This retrospective study examined the relationship between pica and chronic enteropathy (CE) in dogs and cats that presented through emergency services for endoscopic gastric foreign body removal. The researchers hypothesized that animals exhibiting pica might also show clinical and histologic signs of CE, a hypothesis supported by their findings. Among animals that underwent endoscopy and had available referral records, 66% had chronic gastrointestinal signs. All animals that received biopsies (41 in total) showed histologic evidence of chronic enteritis, indicating a strong association between pica and CE. Most animals presented with mild gastric and moderate duodenal inflammation, with lymphoplasmacytic gastritis and enteritis commonly observed. While the severity of Helicobacter spp colonization did not correlate with pica episodes, it did correlate with the severity of gastric inflammation, suggesting a potential role in exacerbating gastrointestinal signs. 

Treatment of Helicobacter spp with triple therapy was associated with the resolution of vomiting in previous studies, supporting its inclusion in treatment plans. Budesonide therapy was administered to a subset of animals, resulting in partial or complete resolution of pica in 83% of the cases that returned for follow-up. However, confounding variables such as concurrent use of gastrointestinal-supportive medications may have influenced the outcomes. Importantly, most of the animals with pica were adults, with an average age of 8 years for dogs and 6 years for cats, and none had other known causes of pica like anemia or endocrine disorders. 

The study suggests that pica should be recognized as a potential clinical sign of CE, especially in adult animals with a history of gastrointestinal signs or repeated episodes of pica. Biopsies during endoscopic foreign body retrieval may be valuable for diagnosis and subsequent treatment. The findings also challenge the notion that inflammation is solely due to foreign bodies, as 20% of animals showed inflammation only in the duodenum. Despite limitations such as the retrospective design, lack of standardized histopathology, and absence of a control group, the results support more proactive diagnostic and therapeutic approaches for suspected CE in animals presenting with pica. Future prospective studies with standardized protocols are needed to further clarify the role of CE in pica and the efficacy of treatments such as budesonide. 

Perez, J., Ford, S., & Lynch, H. (2025). Pica as a clinical sign of a chronic enteropathy in dogs and cats. Journal of the American Veterinary Medical Association https://doi.org/10.2460/javma.25.02.0079 

Bottom line — Good idea to remember this rule out.

Librela Adverse Effects

Osteoarthritis (OA) is the most common chronic pain condition in companion animals, significantly reducing their quality of life and life expectancy. While various treatments exist, many have limited effectiveness or carry risks of severe side effects. Managing chronic pain requires balancing efficacy with safety, a challenge compounded by differing perceptions of risk between veterinarians and pet caregivers. Veterinarians may accept the risks of prescription analgesics more readily, while caregivers may be hesitant, as shown by a 2018 study where over one-fifth of dogs prescribed analgesics did not receive them. 

The emergence of bedinvetmab (Librela™), a monoclonal antibody (mAb) targeting nerve growth factor (NGF), marked a significant development in canine OA treatment. Despite global regulatory approval and widespread adoption, concerns have arisen due to safety signals, particularly neurological and musculoskeletal adverse events (AEs), reported post-marketing. These concerns echo issues found in human clinical trials of similar drugs, where NGF inhibition was linked to rapidly progressive osteoarthritis (RPOA). While human studies attempted to mitigate these risks through strict protocols, adverse outcomes still occurred. 

Post-marketing surveillance is essential because clinical trials can't capture the full range of possible AEs. In December 2024, the FDA alerted veterinarians to safety signals with Librela, using statistical analyses to identify elevated rates of lameness and other disorders. However, these analyses are limited by potential biases, including underreporting and confounding factors. To build on this work, researchers conducted a specialist-led analysis comparing Librela to six other OA drugs. They found that musculoskeletal AEs were reported nine times more frequently with Librela, with total reports exceeding those of all comparator drugs over a 20-year period. Independent expert review of some cases suggested a causal relationship between Librela and joint deterioration. 

The drug's popularity, with over 21 million doses distributed globally, is now shadowed by emerging safety concerns. Negative media attention, regulatory investigations, and growing public discourse have intensified scrutiny. Evaluating the expectedness of such AEs is crucial, using Bayesian methods to assess plausibility based on existing knowledge. Like NSAIDs, which can cause subclinical damage before symptoms appear, NGF inhibitors may lead to serious joint damage that becomes clinically evident only much later. Some current claims that Librela’s AEs are “very rare” may underestimate the real risk due to reliance on sales data. 

Historical regulatory failures, such as the FDA’s early opioid mischaracterizations, illustrate the dangers of bias in safety assessments. Librela’s safety claims, based on limited pre-approval trials involving just a few healthy dogs, fall short when compared to the rigorous human mAb studies. The lack of radiographic screening in pre-approval trials means critical signs of joint damage may have gone undetected, reinforcing the need for robust post-marketing evaluation. 

Initially intending to publish a small case series, the authors broadened their scope to avoid dismissal of severe AEs as outliers. They argue that the same standard used to evaluate NSAID risks—acknowledging subclinical damage—should apply here, especially since cartilage damage is often irreversible. Their analysis of 20 years of musculoskeletal AE data complements the FDA’s short-term approach, capturing longer-latency effects that may not emerge in the immediate post-treatment period. 

Recognizing that expert judgment introduces subjectivity, the adjudication panel was composed of veterinarians without pharmaceutical ties. Their findings underscore gaps in the current pharmacovigilance system, notably the absence of specific diagnostic terms like RPOA, which hinders accurate AE classification and reporting. The authors have formally requested that “RPOA” be added to the VeDDRA terminology, defining it as joint pathology exceeding OA’s typical progression. 

Ultimately, the study underscores a critical point: while bedinvetmab is effective in managing pain, it may also accelerate joint damage. To ensure responsible care, veterinary use of mAbs must be scrutinized with the same rigor applied in human medicine. 

Farrell Mike , Waibel Felix W. A. , Carrera Ines , Spattini Giliola , Clark Louise , Adams Robert J. , Von Pfeil Dirsko J. F. , De Sousa Ricardo J. R. , Villagrà Diego Bobis , Amengual-Vila Maria , Paviotti Annalisa , Quinn Rob , Harper Justin , Clarke Stephen P. , Jordan Christopher J. , Hamilton Michael , Moores Andy P. , Greene Mark Irwin Musculoskeletal adverse events in dogs receiving bedinvetmab (Librela) Frontiers in Veterinary Science VOLUME Volume 12 – 2025 https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets. 2025.1581490 DOI 10.3389/fvets.2025.1581490

Bottom line — An update that needs to be discussed

Head Shaking and Pain in Horses

Trigeminal-mediated headshaking (TMHS) in horses is a condition characterized by neuropathic pain without an identifiable underlying cause. It results from hypersensitivity of the trigeminal nerve, where even mild stimuli such as wind, touch, or light can provoke severe pain. This pain is comparable to trigeminal neuralgia in humans and significantly compromises the horse’s welfare. Affected horses often display abrupt, violent head and neck movements along with behaviors such as snorting, nose rubbing, and lip or tongue movements. While the visible episodes are clearly distressing, the study sought to determine whether horses also experience pain in between these attacks. 

Pain is inherently difficult to quantify in veterinary medicine due to the inability to use self-reporting. Thus, behavioral signs and tools such as the Horse Grimace Scale (HGS), which assesses pain through facial expressions, are crucial. The HGS has been validated in several equine pain contexts and is considered unaffected by emotional states unrelated to pain. This study used the HGS to evaluate pain in horses with TMHS at rest, comparing their scores to healthy horses and those with moderate gastrointestinal pain (colic). Results revealed that TMHS horses had significantly elevated HGS scores even in the absence of visible headshaking, with pain levels comparable to those in horses suffering from moderate colic. This supports the hypothesis that TMHS horses experience persistent pain between attacks. 

The study also examined the usability of the HGS by different observer groups. While experienced evaluators generally scored accurately, less experienced observers overestimated pain in healthy horses and underestimated it in TMHS horses. Nevertheless, observers with general horse knowledge and minimal HGS training could still identify pain in horses with colic reliably, suggesting that the HGS can be a useful tool with adequate familiarization. 

Several limitations were noted, including the small number of observers per group, the brief two-day observation period for TMHS horses, and the subjective classification of pain levels in colic horses. Despite these constraints, intraobserver reliability was good for most facial action units, supporting the HGS’s general effectiveness. 

Overall, the study highlights the need for ongoing, individualized pain assessment in TMHS horses, even outside of active headshaking episodes. It emphasizes that these horses can suffer silently and that their quality of life may be significantly impaired if this persistent pain goes unrecognized and unmanaged. 

Franzen, V., Reisbeck, D., Leibl, Y., Schoster, A. and May, A. (2025), Pain Assessment of Horses With Trigeminal-Mediated Headshaking (TMHS) at Rest Between Episodes. J Vet Intern Med, 39: e70064. https://doi.org/10.1111/jvim.70064 

Bottom line — Individual pain assessment is essential.

Just putting things in perspective …