Zero Pain Reflect: A Comprehensive Review of Pain Management in Canine Osteoarthritis

Understanding Recent Advances in Canine Pain Management

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, allowing you to read the full text. However, we understand that time is limited, so we’ve distilled the essential information you need to know. Additionally, we will explore other relevant papers that provide useful insights.

The aim of this research roundup is to offer veterinary professionals an easy-to-read digest on three significant studies in pain management, all focusing on a common subject area. These research roundups serve as a single point of reference for readers and encourage reflective thinking on the presented topics.

Paper 1: Grapiprant in Osteoarthritis Management

Licensed Indication

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

This study by Rausch-Derra et al. (2016) involved a field study with 285 dogs diagnosed with arthritis. Each dog exhibited clinical signs of osteoarthritis (OA) and radiographic signs in one appendicular joint. Caregivers used the Canine Brief Pain Inventory (CBPI), a validated pain scale for OA, to assess pain levels. Additionally, veterinarians completed a total orthopedic score (TOS) that evaluated lameness, range of motion, and pain on joint palpation.

The primary goal was to document the efficacy of 2mg/kg grapiprant administered SID per os and to evaluate the drug's safety in a clinical population of dogs. The dogs were divided equally into treatment and control groups. Evaluations were conducted using the CBPI every seven days for 28 days, with TOS assessments on days 0, 14, and 28. Success was defined as a reduction of one point in the pain severity score and two points in the pain interference score on the CBPI, as per the validation work for the CBPI.

Among the 262 dogs that completed the study, a statistically significant difference (p = 0.03) was observed in the success rate between the grapiprant group (48.1%) and the control group (31.3%). Dogs treated with grapiprant showed greater improvement in TOS than those on placebo (p < 0.08). Notably, ten dogs in the control group and one in the grapiprant group were removed due to lack of efficacy. The dose range of grapiprant was 1.5-2.9mg/kg, influenced by the tablet size used.

In a placebo-controlled study, a placebo response rate of approximately 20-30% in dogs is typical. However, the difference between placebo and treatment in this study was not substantial, even though it was statistically significant.

A separate study evaluated the long-term safety of grapiprant at various doses over nine months. The investigators noted, ‘Only mild signs of gastrointestinal disturbance, such as occasional vomiting and soft or mucoid feces that occasionally contained blood, were identified in dogs that received grapiprant. Control dogs also exhibited these signs, albeit to a lesser extent. No dogs developed ulcers of the gastrointestinal mucosa.’

It is important to note that there is currently no direct comparison to a non-steroidal anti-inflammatory drug (NSAID) group, indicating that further research is needed before drawing definitive conclusions. This study assessed a range of doses from 0-50mg/kg (with the licensed dose being 2mg/kg), warranting additional work to document adverse effects at the commonly prescribed dose.

Additional Reading

Response to Treatment with Grapiprant as Part of a Standard Multimodal Regimen in Young Dogs with Appendicular Joint Osteoarthritis Associated Pain

Grapiprant was utilized as part of a multimodal pain management regimen in dogs aged 9 months to 4 years 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 included peak vertical force (PVF) from form platform analysis and caregiver-reported outcome measures (CROMs). The results indicated positive response trends, such as reduced pain scores, improved mobility, or decreased inflammation, suggesting that grapiprant effectively contributed to managing osteoarthritis pain in this population. The authors reported, ‘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 align with your clinical experience of using Galliprant?

• Do you routinely include omega-3 supplementation in your treatment plans for OA?

  
  

Paper 2: Enflicoxib for Canine Osteoarthritis

Licensed Indication

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

The study design by Salichs et al. (2022) was a prospective, randomized, blinded, multicenter, non-inferiority trial involving 180 dogs with osteoarthritis. The enflicoxib group included 78 dogs, the mavacoxib group had 80 dogs, and the placebo group consisted of 22 dogs. The study lasted 42 days.

Outcome measures were based on veterinary assessments (Clinical Sum Score, CSS) and caregiver assessments using the CBPI. The primary measure was the overall CSS, which documented that enflicoxib (74% responders) was non-inferior to mavacoxib (68% responders), with both drugs showing superiority over placebo (29% responders). The CBPI responders were enflicoxib 90%, mavacoxib 79%, and placebo 43%. This high placebo rate is notable when using client-reported measures.

No significant differences in adverse events were reported between groups, with most adverse events being mild and gastrointestinal in nature. The authors concluded that enflicoxib is effective and safe for treating pain and inflammation in canine osteoarthritis, making it suitable for all stages of OA.

Additional Reading

Enflicoxib for Post-Surgical Pain Management

Enflicoxib has also been examined for post-surgical pain. In a pilot study by Salichs et al. (2025), enflicoxib was compared to meloxicam for managing pain after orthopedic surgery.

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: Bedinvetmab in Osteoarthritis Management

Licensed Indication

For the alleviation of pain associated with osteoarthritis in dogs.

Link to paper:

Study Design: Double-blind, randomized, placebo-controlled, multicenter 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 was based on the 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 around 25% at all time points.

  
  

CBPI Improvements

Significant improvements were noted in pain severity, pain interference, and overall 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 is safe for long-term use.

Additional Reading

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 the licensing study recruited dogs with all stages of OA. In contrast, the grapiprant study only included dogs with mild or moderate OA, limiting its license to this specific group.

Clinical Utility

Does this help you choose between these 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 orthopedic surgery. A pilot randomized clinical trial. Res Vet Sci. 2025 Sep;193:105804. doi: 10.1016/j.rvsc.2025.105804.