Updated October 29, 2021.  

All osteoarthritis and arthritis sufferers know that this condition can severely affect your ability to lead an active life. Its trademarks are stiff and swollen joints and lots of limiting pain. Standard treatments for relief of pain and stiffness call for cortisol injections, non-steroidal anti-inflammatory drugs (NSAIDs), chondroitin, glucosamine, and other options like biologics. When you’re suffering, all you want to know is this – which drugs are most effective for relieving arthritis pain? This article summarizes the latest research on the effectiveness of arthritis medications and genetic factors that play a role.

Systematic Review of pharmacological treatments for arthritis

A comprehensive review study compared the pain control of over 30 medications used for arthritis pain management. More than 22,000 individuals were tracked over a full year in 42 separate trials, testing both drug effectiveness and drug safety. Of all the treatments studied, two main medications were associated with improved pain (celecoxib and glucosamine sulfate). Below is a summary of key findings from the study and genetic indications of various arthritis treatments.

Non-steroidal anti-inflammatory drugs (NSAIDs) 

NSAIDs are the most widely used pain medications for osteoarthritis. They are the anti-inflammatories you recognize as aspirin, ibuprofen (Advil, Motrin, Midol), naproxen (Aleve, Naprosyn), and celecoxib (Celebrex). Of all the available NSAIDs, celecoxib was the only one to show a reduction in pain scores, although measures indicate only a small improvement in pain. Celecoxib did help with pain management; however, it did not improve physical joint function.

NSAIDs are only recommended for short-term or intermittent use due to increased risk of GI bleeding and cardiovascular events.

Some science behind celecoxib and other NSAIDs:

Celecoxib is a potent COX-2 inhibitor, targeting the enzymes directly responsible for inflammation and pain. It is preferred over non-selective NSAIDs because it’s less likely to affect the digestive system and poses less cardiovascular risk. However, long-term use of celecoxib is still associated with an increased risk of bleeding, particularly in people with slower metabolism of celecoxib. A person’s tolerance and response to NSAIDs are significantly influenced by their genetic drug metabolism. Specifically, celecoxib and other NSAIDs are cleared from the body by the liver enzyme CYP2C9.

• The FDA placed a warning label advising against long-term use of celecoxib in juvenile arthritis patients who are poor CYP2C9 metabolizers.
• New clinical guidelines warn against the use of long-lasting NSAIDs such as tenoxicam, meloxicam and lornoxicam for poor and intermediate CYP2C9 metabolizers.
• People with reduced CYP2C9 function should use the lowest effective dose of celecoxib, ibuprofen and other NSAIDs.
• Naproxen and diclofenac are less affected by CYP2C9 metabolizer status. However, they should be used with caution if prolonged treatment is needed due to the increased risk of heart complications.

New clinical guidelines recommend pharmacogenetic testing for people that need to take NSAIDs frequently.  To find out if you are a poor or intermediate CYP2C9 metabolizer, order the Pillcheck test kit.

Other arthritis treatments could also reduce pain

Glucosamine Sulfate

Glucosamine sulfate, a chemical found naturally in the human body, is involved in building tendons, ligaments, cartilage, and the thick fluid that surrounds joints. It is also a widely used supplement that helps ease pain in people with osteoarthritis.

Patients taking glucosamine sulfate had a bigger reduction in pain scores

The study identified that glucosamine sulfate consistently improved pain levels, physical function, and joint structure – while other glucosamines were not associated with clinical benefit. Glucosamine sulfate must be taken daily to provide ongoing benefit and proved to have the highest probability of being the safest long-term treatment.

More good news: Analysis of the study showed, for the first time, that the protective effect of glucosamine for arthritis pain, function, and joint structure, is more robust than other treatment options such as diclofenac, rofecoxib, and chondroitin sulfate.

What’s more, glucosamine sulfate showed significant improvement in physical function – and, when combined with celecoxib glucosamine, had an even greater impact on reducing chronic pain.  

Hyaluronic Acid and Corticosteroid Injections

Corticosteroid injections directly into the joints resulted in greater pain relief over placebo during the first few weeks of treatment, while hyaluronic acid injections were associated with greater benefit at three and 6-months following the procedure. However, test results show no association of hyaluronic acid with long-term arthritis pain improvement.

Injections using a combination of both hyaluronic acid and corticosteroids had highly variable results.

Other drugs & treatments

In all, 16 drugs and interventions were assessed for structural joint changes. Chondroitin sulfate, strontium ranelate, and glucosamine sulfate were significantly associated with improvement in joint structure. However, chondroitin sulfate had no impact on pain and function. Thus the long-term use of chondroitin sulfate and strontium might not provide meaningful improvement. Strontium ranelate (Protelos), a drug approved for treating osteoporosis in Europe, was also tested. It is not available in Canada due to cardiovascular safety concerns.

Recap of the study findings:

• Glucosamine sulfate consistently improved pain levels, physical function, and joint structure
• Glucosamine sulfate should be taken daily for maximum benefit
• Celecoxib alleviated some pain – but did not improve joint function
• Glucosamine sulfate and celecoxib combined are a more potent pain fighter
• About 20% of people have reduced CYP2C9 function and should use lower doses of celecoxib
• Up to 5% of people are poor CYP2C9 metabolizers and should avoid long-term use of NSAIDs
• Corticosteroid injections helped pain relief in the short term
• Hyaluronic acid injections showed better longer-term relief (3-6 months)
• Chondroitin sulfate had no impact on pain and function but did improve joint structure
• NSAIDs are recommended for short-term pain relief and intermittent use only

Conclusion

This comprehensive study of arthritis pain medications showed that only celecoxib (Celebrex) and glucosamine sulfate have proven to be the most helpful – particularly when used together. Most other drugs, supplements, and even intra-joint injections were found to be less effective in controlling arthritis pain.

If you suffer from chronic arthritis pain, consider Pillcheck to assess whether celecoxib is safe for you. Pillcheck also provides insights on other painkillers, including opioids (oxycodone, tramadol, codeine, morphine) and NSAIDs (celecoxib, diclofenac, flurbiprofen, meloxicam, piroxicam) that can be used to manage arthritis pain.

Selected references:

Gregori D., et al. Association of Pharmacological Treatments With Long-term Pain Control in Patients With Knee Osteoarthritis: A Systematic Review and Meta-analysis JAMA. 2018 Dec 25;320(24):2564-2579.

Theken KN et al., Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2C9 and Nonsteroidal Anti-Inflammatory Drugs (March 2020 update) Clin Pharmacol Ther. 2020 Aug;108(2):191-200

FDA: Table of Pharmacogenomic Biomarkers in Drug Labeling