Osteoarthritis and Use of Non-Steroidal Anti-Inflammatories: The Latest Analysis

By Manijeh “Mani” Berenji

Osteoarthritis (OA) is one of the most common arthritis conditions, afflicting over 32 million of American adults (1). And according to the Osteoarthritis Action Alliance, 62% of those with OA are women (2). People with OA can experience a constellation of joint-related symptoms, as well as greater levels of pain, fatigue, disability, and activity limitations compared to those of similar ages (2,3). And there are significant costs associated with treating OA: In 2013, OA was the 2nd most costly health condition treated in hospitals in the US and was responsible for up to $164 billion in total lost wages (2,4).

When it comes to treating OA, oral non-steroidal anti-inflammatory drugs (NSAIDs) are first-line therapies, followed by paracetamol (acetaminophen) or opioids (5–8). Over the past decade, there has been more evidence to suggest that even though there are improvements in pain and physical function with both opioids and NSAIDs, opioids can cause more significant adverse events, dependency and ultimately death (9,10).

While there have been studies looking at the effectiveness of NSAIDs to treat osteoarthritis pain, these studies primarily looked at drug doses/classes and not specifically clinical therapeutic and functional applications.

In order to provide physicians with up-to-date evidence on the most clinically beneficial medications for osteoarthritis pain, Da Costa and associates assessed the effectiveness and safety of different preparations and doses of NSAIDs, opioids, and paracetamol. The study authors looked at these medications in the treatment of knee and hip osteoarthritis pain and physical function by performing a systematic review and meta-analysis.

After identifying and sorting through the evidence, a total of 92 eligible trials were included. Da Costa and colleagues looked at 90 different active medication preparations (68 for NSAIDs, 19 for opioids, and 3 for paracetamol).

Da Costa and investigators found that out of these 90 preparations, only 5 (diclofenac 150 mg/day, etoricoxib 60 and 90 mg/day, and rofecoxib 25 and 50 mg/day) had over 99% probability of demonstrated treatment effects covering pain as well as overall function. When analyzing topicals, topical diclofenac (at 70–81 and 140–160 mg/day dosing) had over 92.3% probability of demonstrated treatment effects. Opioids as a whole had less than 53% probability of demonstrated treatment effects.

In conclusion, the study investigators concluded that etoricoxib 60mg/day and diclofenac 150mg/day are the most effect oral NSAIDs for pain and function for OA patients but these treatments are not meant for long-term use because of the slight increased risk of side effects. For optimal dosing and least amount of side effects, topical diclofenac 70–81 mg/day was the most therapeutic dosing and is the recommended first-line pharmacological treatment for knee OA. Opioids are not recommended because of the harm and notable adverse effects these medications can cause in the short- and long-terms.

References:

1. United States Bone and Joint Initiative. The Burden of Musculoskeletal Diseases in the United States (BMUS). In: In. Fourth ed. Rosemont, IL. 2018: Available at https://www.boneandjointburden.org/fourth-edition. Accessed on 28 November 2021.

2. Osteoarthritis Action Alliance. “Osteoarthritis Prevention & Management in Primary Care OA PREVALENCE AND BURDEN.” Available at: https://oaaction.unc.edu/oa-module/oa-prevalence-and-burden/. Accessed on 28 November 2021.

3. Osteoarthritis Research Society International. Osteoarthritis: A Serious Disease, submitted to the U.S. Food and Drug Administration. 2016. Available at: https://oarsi.org/sites/default/files/docs/2016/oarsi_white_paper_oa_serious_disease_121416_1.pdf. Accessed 28 November 2021.

4. Centers for Disease Control and Prevention. Arthritis Cost Statistics Available at https://www.cdc.gov/arthritis/data_statistics/cost.htm. Published 2018. Accessed 28 November 2021.

5. da Costa B R, Pereira T V, Saadat P, Rudnicki M, Iskander S M, Bodmer N S et al. Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: network meta-analysis. BMJ 2021; 375 :n2321.

6. National Clinical Guideline Centre (UK). Osteoarthritis: Care and Management in Adults. London: National Institute for Health and Care Excellence (UK), 2014. Available at: https://www.ncbi.nlm.nih.gov/books/NBK248069/. Accessed 28 November 2021.

7. 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 Care Res (Hoboken)2020;72:149–62.

8. Bannuru RR, Osani MC, Vaysbrot EE, et. al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage 2019;27:1578–89.

9. Krebs EE, Gravely A, Nugent S, et. al. Effect of opioid vs nonopioid medications on pain-related function in patients with chronic back pain or hip or knee osteoarthritis pain: The SPACE randomized clinical trial. JAMA 2018;319:872–82.

10. Busse JW, Wang L, Kamaleldin M, et. al. Opioids for chronic noncancer pain: a systematic review and meta-analysis. JAMA 2018;320:2448–60.