Librela Benefit-Risk Balance - What Vets Need to Know
Scales on dark background representing benefit-risk balance
No medicine can be assumed to be risk-free. Every time an animal is treated a vet must ask: do the expected benefits from the intervention outweigh its disadvantages, which include potential adverse effects and other factors such as the need for monitoring?
Benefit is also a matter of probability
The way information about medicines is presented tends to promote the idea that the benefits are absolute (all treated animals will benefit) and the adverse effects a probability (only some will experience them). For example, the product information for Librela (bedinvetmab) describes the benefit as the "alleviation of pain associated with osteoarthritis in dogs", whereas, the adverse effects are listed with a specific probability, such as polyuria occurring in 1 to 10 out of 10,000 treated animals). (Librela SPC [GB]). But benefit is also a matter of probability. In the clinical trials of Librela, pain was alleviated in just under half of treated dogs.
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Regulators assess benefit-risk balance in a population
When deciding to grant or reject a marketing authorisation for a medicine, the regulator (the Veterinary Medicines Directorate [VMD] in Great Britain) determines if the "benefit-risk balance" is favourable/positive (VMR 2013, as amended). It assesses the quality, safety and efficacy of the product, taking into account the strength of the evidence from clinical trials, the size and probability of the benefits, the profile of the enrolled animals (which often exclude those with specific characteristics), the adverse effects identified in trials, and potential wider harms (to people and the environment). The regulator's assessment of benefit-risk is qualitative, partially subjective and cannot be expressed as a value.
Benefit-risk balance is not static
The clinical trials performed to gain a marketing authorisation are not usually designed to study the adverse effects of medicines: they include a limited number of animals and are of limited duration. In pre-marketing trials of Librela a total of 559 dogs were treated for 12 weeks. Therefore only the most common adverse effects will have been identified in the early days of marketing. It can take years before rare and possibly serious adverse effects are discovered, through case reports, pharmacovigilance and perhaps pharmacoepidemiology. This means that the benefit-risk balance of a medicine can change over time.
When Librela was first marketed (in 2021 in the UK), the only adverse effect attributed to it was mild reactions at the injection site (e.g. heat and swelling), which was reported as uncommon (i.e. affecting between 1 and 10 in 1000 treated dogs). In the intervening years, other adverse effects have emerged including very rare, but potentially severe and irreversible adverse effects on joints.
Such new information about harms should trigger a reappraisal of the benefit-risk balance, and in February of this year the VMD declared it was satisfied that the overall benefits of Librela continue to outweigh the risks for most dogs treated with the medicine (VMD 2026). So, while the overall benefit-risk balance has actually changed since the product was first authorised, this cannot be accurately depicted in the regulator's shorthand decision, only understood from reading the revised text of the product's summary of product characteristics (SPC).
Benefit-risk balance must be determined for each patient
While the regulator makes a decision about benefit-risk at a population level, that judgement cannot predict exactly what will happen when an individual animal is treated. It is up to the individual vet to use the information to determine the benefit-risk balance in the context of the individual patient’s and client’s characteristics.
To be able to do this, vets need clear, up-to-date information on the probability and size of benefit, the range of adverse effects, and the remaining uncertainties. Veterinary Prescriber provides the information to support such informed decisions and conversations with clients. We do this by systematically searching for, and appraising the evidence, and providing an impartial summary in the context of clinical practice.
Veterinary Prescriber’s full, updated review of Librela, including the latest evidence on adverse effects, is available to subscribers.