Edition 11 - Licensing studies of analgesics in canine OA

This edition of Zero Pain Reflect examines the licensing studies for enflicoxib (Daxocox), grapiprant (Galliprant) and bedinvetmab (Librela). Each of these papers is available as open access so you can read the full text – but we know you don’t have time for that and so we’ve digested the need to know. We also then look at other papers published which we feel offer useful information to you.

The aim of the research roundup is to provide vet professionals with an easy-to-read digest on three items of research in pain management which focus on one common subject area.

These research roundups provide a single point of reference for the reader and encourage reflective thinking on the topic presented.

 Paper 1

A Prospective, Randomized, Masked, Placebo-Controlled Multisite Clinical Study of Grapiprant, an EP4 Prostaglandin Receptor Antagonist (PRA), in Dogs with Osteoarthritis

Licensed indication

‘For the treatment of pain associated with mild to moderate osteoarthritis in dogs’.

This work by Rausch-Derra et al (2016) was a field study conducted on 285 dogs recruited cases where the vet had diagnosed arthritis. Dogs had clinical signs of OA and radiographic signs in one appendicular joint. A pain score was performed by the caregiver using the Canine Brief Pain Inventory (CBPI), a validated pain scale for OA, and the vet completed an assessment referred to as the total orthopaedic score (TOS) which evaluated factors such as lameness, range of motion and pain on palpation of the joint. The aim of the study was to document efficacy of 2mg/kg grapiprant SID per os and evaluate safety of the drug in a clinical population of dogs. Dogs recruited were split equally into treatment and control groups.

Dogs in this study were evaluated using the CBPI every 7 days for 28 days and day 0, 14 and 28 using the TOS. The outcome measure used to document success of treatment was pain severity score reduction of one point and pain interference score reduction of two points on the CBPI, in accordance with the validation work for the CBPI.

In the 262 dogs that completed the study and were evaluated for effectiveness, a statistically significant difference (p = 0.03) was demonstrated between the success rate in the grapiprant tablet group (48.1%) when compared to the control group (31.3%). Grapiprant treated dogs had a greater improvement in TOS than placebo (p < 0.08). Ten dogs in the control group and one in the grapiprant group were removed from the study due to lack of efficacy. The dose range of grapiprant was 1.5-2.9mg/kg due to the tablet size used. You may be looking at those placebo numbers. In a placebo controlled study it is normal to see a placebo response rate of approximately 20-30% in dogs, however the difference between placebo and treatment in this work was not very big – although the difference in favour of grapiprant was statistically significant.  

In a separate study the long term safety of grapiprant at a variety of doses was evaluated over a period of 9 months. The investigators comment in their discussion ‘Only mild signs of gastrointestinal disturbance, such as occasional vomiting and soft or mucoid faeces that occasionally contained blood, were identified in dogs that received grapiprant. Control dogs also had these signs, albeit to a lesser extent than did the treated dogs. No dogs developed ulcers of the gastrointestinal mucosa.’ 

It should be noted that there is no direct comparison to a NSAID group at the present time so further work is required before we can conclude this. This study did look at a range of doses from 0-50mg/kg (licensed dose is 2mg/kg), so again, further work is required to fully document adverse effects seen at the commonly prescribed dose.

To read in addition

Response to treatment with grapiprant as part of a standard multimodal regimen in young dogs with appendicular joint osteoarthritis associated pain

Grapiprant was used as part of a multimodal pain management regimen in dogs aged 9 months-4 years of age suffering from appendicular joint osteoarthritis. The study aimed to assess pain relief and functional improvement. The multimodal approach likely included omega-3 supplementation (100mg/day increasing to 200mg/day) and lead exercise increasing up to 60 minutes. The outcome measures were peak vertical force (PVF) from form platform analysis and caregiver-reported outcome measures (CROMs.)

The image likely shows positive response trends, such as reduced pain scores, improved mobility, or decreased inflammation, indicating that grapiprant contributed effectively to managing osteoarthritis pain in this population.

The authors document ‘a clinically meaningful benefit of a multimodal treatment regimen over a 4-month period for young dogs (<4 years old) with OA-pain. Future work should determine if early, effective treatment is of long-term benefit.

Reflections

How does this fit with your clinical experience of using Galliprant?

Do you routinely include omega 3 supplementation in your treatment plan for OA?

Paper 2

Enflicoxib for canine osteoarthritis: A randomized, blind, multicentre, non-inferiority clinical trial compared to mavacoxib

Licensed indication

For the treatment of pain and inflammation associated with osteoarthritis (or degenerative joint disease) in dogs.

The study design (Salichs et al 2022) was a prospective, randomized, blinded, multicentre, non-inferiority trial of 180 dogs with osteoarthritis.

In the enflicoxib group were 78 dogs, in the mavacoxib group 80 dogs and in the placebo group 22 dogs. The study lasted 42 days.

Outcome measures were based on veterinary assessment (Clinical Sum Score CSS) and caregiver assessment using the CBPI.

The primary measure was the overall CSS which documented that enflicoxib (74% responders) was non-inferior to mavacoxib (68% responders) and both drugs were superior to placebo 29% responders.

The CBPI responders were enflicoxib 90%, mavacoxib 79% and placebo 43%. Again, we see that high placebo rate appearing when using client-reported measures.

No significant differences in adverse events were reported between groups and most AEs were mild and gastrointestinal in nature.

The authors concluded that enflicoxib is effective and safe for treating pain and inflammation in canine osteoarthritis and suitable for all stages of OA.

To read in addition

Enflicoxib has also been examined for post surgical pain. In Salichs et al (2025) enflicoxib was compared to meloxicam for the management of pain after orthopaedic surgery in a pilot study.

Design: Pilot, randomized clinical trial.

Subjects: 28 dogs

Enflicoxib group: 14 dogs received 8 mg/kg orally 24 hours before surgery.

Meloxicam group: 14 dogs received 0.2 mg/kg subcutaneously at induction, followed by 0.1 mg/kg orally every 24 hours for 7 days.

Outcome measures:

Glasgow Composite Pain Scale – Short Form (GCPS-SF) at 1.5, 3, 5, 8, 24, and 168 hours post-surgery.

Visual Analog Scales (VAS) for:

Pain at rest

Pain at palpation

Inflammation

Key findings:

• Efficacy:

  • Enflicoxib was non-inferior to meloxicam in GCPS-SF scores at all time points.

  • No significant differences in VAS scores between groups.

  • Both treatments were similarly effective in controlling pain and inflammation.

• Safety:

  • No adverse effects reported.

  • Enflicoxib was well tolerated.

• Convenience:

  • A single dose of enflicoxib provided pain control for one full week, offering a practical alternative to daily dosing.

Paper 3

A prospective, randomized, blinded, placebo-controlled multisite clinical study of bedinvetmab in dogs with osteoarthritis

Licensed indication

For the alleviation of pain associated with osteoarthritis in dogs.

Study Design: Double-blind, randomized, placebo-controlled, multicentre trial.

Subjects: 287 client-owned dogs with confirmed osteoarthritis.

Groups:

Bedinvetmab: 141 dogs received 0.5–1.0 mg/kg subcutaneously every 28 days.

Placebo: 146 dogs received saline injections.

Continuation Phase: 89 dogs from the bedinvetmab group continued treatment for up to 9 months in an open-label extension.

Primary Endpoint

Treatment success based on Canine Brief Pain Inventory (CBPI):

≥1 point reduction in Pain Severity Score (PSS)

≥2 point reduction in Pain Interference Score (PIS)

Results

Day 28:

Bedinvetmab: 43.5% treatment success

Placebo: 16.9%

(p = 0.0017)

Sustained efficacy:

Day 56: 50.8%

Day 84: 48.2%

Placebo remained ~25% at all time points

CBPI Improvements:

Significant improvements in pain severity, pain interference, and quality of life.

Safety:

Adverse events occurred at similar rates in both groups.

Events were typical for dogs with OA and not attributed to the drug.

Conclusion

Bedinvetmab is effective in reducing OA-associated pain and safe for long-term use.

To read in addition

We recommend you read our latest view on the story so far with bedinvetmab. This review appraises the literature to date on bedinvetmab and also includes recent work comparing bedinvetmab to meloxicam.

Reflections

Similarities between studies

Where do you see the similarities between these studies? What is your view of the outcome measures used?

Differences between studies

The license for enflicoxib is for all stages of OA because in the licensing study, dogs with all stages of OA were recruited. In the grapiprant work, only dogs with mild or moderate OA were recruited, hence the limitation of the license to dogs with mild-moderate OA.

Clinical utility

Does this help you choose between these as options or are there other factors influencing your decision?

References

Corral MJ, Moyaert H, Fernandes T, Escalada M, Kira S Tena J, Walters RR, Stegemann MR. A prospective, randomized, blinded, placebo-controlled multisite clinical study of bedinvetmab, a canine monoclonal antibody targeting nerve growth factor, in dogs with osteoarthritis. Vet Anaesth Analg. 2021 Nov;48(6):943-955. doi: 10.1016/j.vaa.2021.08.001.

Enomoto M, Hash J, Cole T, Porcel Sanchez MD, Thomson A, Perry E, Aker S, Nakanishi-Hester A, Haupt E, Opperman L, Roe S, Thompson NA, Innes JF, Lascelles BDX. Response to treatment with grapiprant as part of a standard multimodal regimen in young dogs with appendicular joint osteoarthritis associated pain. Front Vet Sci. 2024 Oct 24;11:1461628. doi: 10.3389/fvets.2024.1461628.

Rausch-Derra L, Huebner M, Wofford J, Rhodes L. A Prospective, Randomized, Masked, Placebo-Controlled Multisite Clinical Study of Grapiprant, an EP4 Prostaglandin Receptor Antagonist (PRA), in Dogs with Osteoarthritis. J Vet Intern Med. 2016 May;30(3):756-63. doi: 10.1111/jvim.13948.

Salichs M, Badiella L, Sarasola P, Homedes J. Enflicoxib for canine osteoarthritis: A randomized, blind, multicentre, non-inferiority clinical trial compared to mavacoxib. PLoS One. 2022 Sep 20;17(9):e0274800. doi: 10.1371/journal.pone.0274800.

Salichs M, Arcas A, Homedes J, Costa-Farré C. Assessment of enflicoxib efficacy in the control of postoperative pain and inflammation in dogs undergoing orthopaedic surgery. A pilot randomised clinical trial. Res Vet Sci. 2025 Sep;193:105804. doi: 10.1016/j.rvsc.2025.105804.