Arthritis pain? The best meds for relief are...

Osteoarthritis, the most common type of arthritis, causes stiff, painful joints that can make it hard to stay active. It mainly affects the knees, hips and hands. There are many treatment options, from exercise to pills, creams, supplements and injections, and it can be hard to know which ones work. This article explains what current guidelines and research show, and how your genes, especially CYP2C9, affect the safety of common anti-inflammatory painkillers.

This article focuses on osteoarthritis. Rheumatoid arthritis and other inflammatory types of arthritis are treated differently, often with disease-modifying drugs and biologics.

What do guidelines recommend for osteoarthritis pain?

The 2019 American College of Rheumatology/Arthritis Foundation guideline gives its strongest recommendations to:

• Exercise, including walking, strength training and tai chi.
• Weight loss for people with knee or hip osteoarthritis who are overweight.
• Self-management programs, a cane and, for the knee, a brace.
• NSAID creams and gels (topical NSAIDs) for knee osteoarthritis.
• NSAID pills (oral NSAIDs), at the lowest effective dose for the shortest time.
• Corticosteroid injections into the knee or hip for short-term relief.

Acetaminophen (Tylenol), duloxetine and tramadol are conditionally recommended for some people. The guideline recommends against other opioids for osteoarthritis.

Which NSAIDs work best for arthritis pain?

NSAIDs such as ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn), diclofenac (Voltaren) and celecoxib (Celebrex) reduce pain and inflammation. Diclofenac gel is a good option for knee and hand osteoarthritis because little of the drug reaches the bloodstream.

Celecoxib is gentler on the stomach than older NSAIDs. In the large PRECISION trial of more than 24,000 people with arthritis, celecoxib caused fewer stomach and bowel complications than ibuprofen or naproxen, and its risk of heart attack and stroke was similar, not lower. All NSAID pills can raise the risk of stomach bleeding, kidney problems and heart problems, especially with long-term use, so they are best used at the lowest effective dose and reviewed regularly. Read more in Are you a Tylenol or Advil person? Alleviating pain through genetics.

Do glucosamine and chondroitin help?

The evidence is mixed. A 2018 analysis of 47 long-term trials in knee osteoarthritis linked glucosamine sulfate and celecoxib to less pain, and glucosamine sulfate, chondroitin sulfate and strontium ranelate to less narrowing of the joint space on X-rays. However, the authors noted large uncertainty in all the estimates, and several of them worked for a company that makes glucosamine sulfate. The American College of Rheumatology recommends against glucosamine for knee and hip osteoarthritis, and against chondroitin except for hand osteoarthritis. If you want to try glucosamine sulfate, discuss it with your health care provider.

What about injections?

Corticosteroid injections can relieve knee and hip pain for several weeks. Hyaluronic acid injections give inconsistent results, and the American College of Rheumatology does not recommend them for knee osteoarthritis. Strontium ranelate, an osteoporosis drug once studied for arthritis, is not available in Canada.

How do genes affect NSAIDs?

Celecoxib, ibuprofen, flurbiprofen, meloxicam, piroxicam and several other NSAIDs are broken down by the liver enzyme CYP2C9. People who are intermediate or poor CYP2C9 metabolizers clear these drugs more slowly, which raises drug levels and may increase the risk of side effects such as stomach bleeding and high blood pressure. The CPIC NSAID guideline recommends:

• Celecoxib, ibuprofen, flurbiprofen and lornoxicam: intermediate metabolizers should start at the lowest recommended dose; poor metabolizers should start at 25% to 50% of the lowest dose or use another drug.
• Meloxicam: intermediate metabolizers should use half of the lowest dose or another drug; poor metabolizers should use another drug.
• Piroxicam and tenoxicam: long-acting NSAIDs that intermediate and poor metabolizers should avoid.
• Naproxen, diclofenac and aspirin: there is not enough evidence for genetic dosing recommendations.

Health Canada and FDA labels for celecoxib also advise a lower dose for poor CYP2C9 metabolizers. Read more about genes and other arthritis medications, including opioids, methotrexate and azathioprine, in Worried about side effects of arthritis medications?

Can a pharmacogenetic test help?

Pillcheck reports CYP2C9 and other genes that affect NSAIDs, opioids such as codeine and tramadol, duloxetine and many other medications, with 355 medications in total. A Pillcheck pharmacist reviews your results and all your medications and recommends safer options and doses to discuss with your prescriber.

Summary

• Exercise, weight loss, NSAIDs and corticosteroid injections are the best-supported treatments for osteoarthritis pain.
• NSAID creams and gels are a good option for knee and hand pain; NSAID pills should be used at the lowest effective dose.
• Celecoxib is gentler on the stomach but has a heart risk similar to ibuprofen and naproxen.
• The evidence for glucosamine and chondroitin is mixed, and major guidelines do not recommend them for knee or hip osteoarthritis.
• CYP2C9 genes affect celecoxib, ibuprofen, meloxicam and piroxicam, and CPIC gives dosing recommendations.

Frequently asked questions

What is the best medication for arthritis pain?

For osteoarthritis, NSAIDs (as creams, gels or pills) are among the most effective medications, along with exercise and weight loss. The best choice depends on your other health conditions, your other medications and your genes.

Is celecoxib safer than ibuprofen?

Celecoxib causes fewer stomach and bowel problems, but its heart risk is similar to ibuprofen and naproxen at moderate doses.

Does glucosamine work for knee arthritis?

Some studies suggest glucosamine sulfate may modestly reduce pain, but the evidence is uncertain and the American College of Rheumatology recommends against it for knee and hip osteoarthritis.

How do my genes affect NSAIDs?

CYP2C9 breaks down celecoxib, ibuprofen, meloxicam and other NSAIDs. Poor and intermediate metabolizers may need a lower dose or a different drug.

Can a DNA test help me choose a painkiller?

Yes. A pharmacogenetic test can show how you handle NSAIDs, opioids and other pain medications, helping your prescriber choose a safer option and dose.

References

Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Rheumatol. 2020;72(2):220-233.

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

Nissen SE, Yeomans ND, Solomon DH, et al. Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis. N Engl J Med. 2016;375(26):2519-2529.

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