In dogs diagnosed with osteoarthritis, is meloxicam superior to carprofen for reducing patient discomfort?

a Knowledge Summary by

Lesca Monica Sofyan DVM student ^1*

¹Sydney School of Veterinary Science, The University of Sydney, Head Office JD Steward Building University of Sydney, NSW, 2006, Australia
^*Corresponding Author (lesca.sofyan.xx@hotmail.com)

Clinical scenario

A 10-year-old Rottweiler cross has been diagnosed with canine osteoarthritis, specifically affecting the hip joints. His owner asks what the patient can be treated with to reduce discomfort and pain, particularly during walks. You recommend non-steroidal anti-inflammatory drugs (NSAIDs). You present the different types of NSAIDs available in your clinic, which are meloxicam and carprofen. The owner asks if one is superior to the other and whichever one that is, he will purchase. Ensuring that you are providing gold standard treatment, you want to ensure that you are providing an NSAID that has proven to be the most effective.

The evidence

Only one randomised controlled clinical trial compared the level of efficacy between meloxicam and carprofen in reducing pain and discomfort in dogs diagnosed with osteoarthritis. An additional study was evaluated but this had very small case numbers, no control group and gave no detailed statistical analysis. Both articles directly compared meloxicam and carprofen along with another treatment (either a nutraceutical or another NSAID) in reducing pain and discomfort for dogs diagnosed with osteoarthritis.

Summary of the evidence

Appraisal, application and reflection

Both studies obtained observational evaluations from owners regarding their dog’s mobility and gait during treatment although, this qualitative approach was more predominant in the study by Mariana et al. (2013). Whilst this is beneficial in providing primary insight on owner’s experiences, it does possess weaknesses. Qualitative evaluations are not narrowly focused on a specific question³. The observations made by owners are not controlled in a clinical setting and thus, selective bias may be introduced into the study as an owner may favour one NSAID over another (e.g. meloxicam over carprofen). Furthermore, participants may misinterpret criteria and guidelines and thus deliver incorrect or vague answers. Metrology instrument testing for canine osteoarthritis are now available and have been clinically validated to effectively assess the quality of life and locomotive function in dogs with orthopaedic related disorders⁴.  One of the instruments that may have been useful for Mariana et al. (2013) and for future related studies is the Canine Orthopaedic Index (COI)⁴. The COI assesses the following four domains – stiffness, function, gait and quality of life for patients diagnosed with osteoarthritis or related orthopaedic disorders. The outcome provides a quantifiable assessment that clinicians and researchers can use to assess the efficacy of treatment provided.

The sample sizes in both studies were considerably small. Both studies did not provide details on how sample size was determined for it to be considered appropriate and adequate for clinical research. In validated scientific research and clinical trials, sample size should be determined from a power analysis. Appropriate sample sizes are essential in providing a true representation of an underlying population and ensuring that the clinical question proposed allows for a valid statistical analysis⁵. Inadequate sized studies are underpowered and may lead to statistical error and invalid conclusions.

Blinding is an important and distinct feature in randomised controlled trials to reduce selection bias from affecting results, which both studies did^1,2,6,7. Patients and evaluators assigned to a treatment with knowledge and no concealment may deliberately select to disapprove or approve a treatment based on personal beliefs and influential factors^6,7. Clinically, it is common for practitioners to favour a particular therapeutic drug over another for certain procedures. The lack of a control group in the Mariana et al. (2013) study also meant there was no baseline to compare and assess the efficacy of the intervention (i.e. meloxicam or carprofen) that is essential in clinical trials ^5,6.

Statistical analysis is a crucial foundation in evidence-based clinical practice and should be implemented in all clinical trials and research⁸. The small sample size, lack of statistical analysis and poor eligibility criteria in the study by Mariana et al. (2013) may have meant that the results retrieved from the study were largely due to chance, thus limiting valid conclusions to be drawn. The application of statistical analysis (e.g. use of p-values and confidence intervals) aids in building a solid and sound evidence to ensure that the clinical courses and treatments tested are most likely to follow and have the same result⁸.

Moreau et al.’s (2003) application of analysing GFR strengthened the findings of the study. Analysis of GFR is a non-invasive method and objective measurement of gait evaluation^9,10. It accurately assesses between normal and abnormal gait, identifying characteristic features in gait abnormalities⁹. The findings of the GFR in Moreau et al.’s study (2003) was accompanied with the owner’s assessment of their dog’s mobility, representing a quantitative and qualitative approach to the study and orthopaedic surgeon assessment. The combined use of a quantitative and qualitative approach as used in Moreau et al.’s (2003) study is advocated in clinical trials as it neutralises flaws that may be present in one methodology and strengthens and validates results^9,10,11. The results of the GFR can be corresponded to the owner’s assessment in regard to treatment response.

Consistency was adhered to in both methodological approaches where there was no note on potential external interferences (e.g. weight loss, hydrotherapy, physiotherapy, chondroitin sulphate injections) that may have potentially skewed the results of the studies.

An additional finding in the Moreau et al. (2003) study worth noting was a case whereby a patient was diagnosed with toxic idiosyncratic hepatitis to the carprofen treatment group. Side effects from the use of long-term NSAIDs are a significant concern amongst owners and small animal practitioners. Mariana et al. (2013) claimed meloxicam was better tolerated than carprofen due to the differing pathogenesis of the two treatments, as meloxicam is a COX-2 inhibitor and carprofen is a COX-1 inhibitor². However, this is questionable as current evidence recognises carprofen preferentially inhibiting the COX-2 enzyme pathway⁹.

 Despite the finding in Moreau et al. (2013) study, all dosages must be adjusted or lowered to the safest level when treating any case of osteoarticular inflammation. The dose range of 0.3 mg/kg for meloxicam used in the Mariana et al. (2013) study is actually higher than what is recommended⁹. The recommended meloxicam initial dose is 0.2 mg/kg followed by a maintenance dose of 0.1 mg/kg post-orally (PO) every 24 hours⁹. In Monteir-Steagall et al.’s (2013) systematic review of the drug induced adverse effects found variable results on the number of common adverse effects encountered from carprofen and meloxicam¹³. Across the high strength of evidence, both meloxicam and carprofen induced adverse side effects including vomiting and diarrhoea as the two most common, as well as anorexia, lethargy, diarrhoea and melena¹³. Meloxicam is available in both tablet and liquid formulation whilst carprofen is available only in tablet form. Dogs that do not tolerate well with tablet administration may be provided the alternative of the meloxicam liquid formulation, but this may be limited if unwanted side effects have been experienced with dogs on meloxicam. Therefore, whether practitioners and clients choose to prescribe carprofen and meloxicam for managing osteoarthritis, the health parameters and status of the patient on the treatment should be independently and regularly monitored to detect early unwanted side effects.

Both studies found patients diagnosed with osteoarthritis treated with either meloxicam or carprofen indeed improved articular motility. However, the absence of validated metrology instruments, poor eligibility and inclusion criteria, lack of statistical analysis and poor sample sizes does mean the studies are not universally and scientifically valid to conclude that the benefits of meloxicam are superior to carprofen.

The two studies are nonetheless good foundations for a much wider and future study, such as a prospective randomised controlled trial with adequate population sizes, proper statistical analysis and validated metrology instruments to potentially assess the superiority of one NSAID to another.

Meloxicam or carprofen evidently improve patients with osteoarthritis but the evidence to scientifically conclude that meloxicam is superior to carprofen is weak. The selection of an NSAID by small animal practitioners for patients diagnosed with osteoarthritis should thus be selected on other variables such as suitability for the patient signalment (e.g. dosage levels, history of side effects if previously medicated on an NSAID), owner’s satisfaction (e.g. tablet vs liquid form, cost) and veterinarian’s discretion.

Methodology Section

Search Strategy
Databases searched and dates covered:	PubMed database accessed via the NCBI platform (1910–2019) CAB Abstracts database via Web of Science (1973–2019)
Search strategy:	((((osteoarthritis OR arthritis OR OA OR osteo-arthritis)) AND (canine OR canines OR dogs OR dogs)) AND (Meloxicam OR Metacam OR Loxicom OR Loxioral OR Melonex OR Meloxidy OR Mobic OR Mobicox OR Orocam)) AND (Carprofen OR Rimadyl OR Novox)
Dates searches performed:	28 Aug 2019

Exclusion / Inclusion Criteria
Exclusion:	Articles not written in English Articles not associated with the efficacy of meloxicam and carprofen for canine osteoarthritis Case reports Case studies Book chapters Conferences Systematic reviews
Inclusion:	Meta-analysis Randomised controlled study

Search Outcome
Database	Number of results	Excluded – systematic reviews	Excluded – did not relate directly to the factors of PICO	Excluded – case reports and studies	Excluded – book chapters	Excluded – not written in English	Excluded – conferences	Total relevant papers
PubMed	9	3	5	0	0	0	0	1
CAB Abstracts	19	1	13	0	0	1	2	2
Total relevant papers when duplicates removed								2

The author declares no conflicts of interest.

However, the author would like to greatly thank Bridget Sheppard and Jennifer Morris for their assistance and guidance in this publication, the reviewers (Clare Boulton, Andy Morris and Robert Pettitt) and the team of the journal for providing this opportunity.

Lastly but not least, the author would like to dedicate this paper to Matt Fotheringham and in memory of Sefton Fotheringham for inspiring the clinical question to hopefully aid future clients and patients alike.

1. Moreau, M., Dupuis, J., Bonneau, N. H. & Desnoyers, M. (2003). Clinical evaluation of a nutraceutical, carprofen and meloxicam for the treatment of dogs with osteoarthritis. Veterinary Record, 152(11): 323–329. DOI: http://dx.doi.org/10.1136/vr.152.11.323
2. Mariana, G., Valentin, N., Raluca, M. & Hritcu, D-L. (2013). Comparative evaluation on the efficiency and tolerability of three NSAIDs used in locomotive osteoarticular inflammations in dog. Scholars Journals of Agriculture and Veterinary Sciences. 56: 274–282.
3. Choy, L. T. (2014). The Strengths and Weaknesses of Research Methodology: Comparison and Complimentary between Qualitative and Quantitative Approaches. Journal of HumanIties and SocIal Science, 19(4): 99–104. DOI: http://dx.doi.org/9790/0837-194399104
4. Cook, J. (2014). Canine Orthopedic Outcome Measures Program: Where Are We Now? Veterinary Surgery, 43(3): 229–231. DOI: https://doi.org/10.1111/j.1532-950X.2014.12167.x
5. Suresh, K. P. & Chandrashekara, S. (2012). Sample size estimation and power analysis for clinical research studies. Journal of Human Reproductive Science, 5(1): 7–13. DOI: https://doi.org/4103/0974-1208.97779
6. Bang, H., Ni, L. & Clarence, E. D. (2004). Assessment of blinding in clinical trials. Controlled Clinical Trials, 25(2): 143–156. DOI: https://doi.org/10.1016/j.cct.2003.10.016
7. Juni, P., Altman, D.G. & Egger, M. (2001). Assessing the quality of controlled clinical trials. BMJ, 323: 42–46. DOI: https://doi.org/10.1136/bmj.323.7303.42
8. Barkan, H. (2015). Statistics in clinical research: Important considerations. Annals of Cardiac Anaesthesia, 18(1): 74–82. DOI: http://dx.doi.org/10.4103/0971-9784.148325
9. Ramsey, I. (2017). Small Animal Formulary 9^th Edition – Part A: Canine and Feline. 59.
10. Anderson, M. A. & Mann, F. A. (1994). Force plate analysis: a non-invasive tool for gait evaluation. Compendium on Continuing Education for the Practicing Veterinarian, 16: 857-866.
11. McLaughlin, R. M. (2001). Kinetic and Kinematic Gait Analysis in Dogs. Veterinary Clinics of North America: Small Animal Practice, 31(1): 193–201. DOI: https://doi.org/10,.1016/S0195-5616(01)50045-5
12. Hussein, A. (2009). The Use of Triangulation in Social Sciences Research: Can qualitative and quantitative methods be combined? Journal of Social Work Practice, 01–12.
13. Monteiro-Steagall, B. P., Steagall P. M. V. & Lascelles, B. D. X. (2013). Systemic Review of Nonsteroidal Anti-Inflammatory Drug-Induced Adverse Effects in Dogs. Journal of Veterinary Internal Medicine, 27(5): 1011–1019. DOI: http://doi.org/10.1111/jvim.12127