By Pat Anson, PNN Editor

Ibuprofen, naproxen and other non-steroidal anti-inflammatory drugs (NSAIDs) are often recommended as safer and more effective pain relievers than opioids. As evidence, anti-opioid activists often cite a 2018 study that found NSAIDs worked “significantly better” than opioids in reducing pain intensity for patients with osteoarthritis.

That study by VA researcher Erin Krebs, MD, is cited nearly a dozen times in the newly revised CDC opioid guideline, which recommends that patients avoid opioids and use topical or oral NSAIDs for osteoarthritis pain.

But according to a new long-term study, NSAIDs may actually worsen inflammation and weaken cartilage in patients with knee osteoarthritis, contributing to a painful joint condition called synovitis.

“The goal of our study was to analyze whether NSAID treatment influences the development or progression of synovitis and to investigate whether cartilage imaging biomarkers, which reflect changes in osteoarthritis, are impacted by NSAID treatment,” says lead author, Johanna Luitjens, MD, a postdoctoral scholar in the Department of Radiology and Biomedical Imaging at the University of California, San Francisco.

“NSAIDs are frequently used to treat pain, but it is still an open discussion of how NSAID use influences outcomes for osteoarthritis patients. In particular, the impact of NSAIDs on synovitis, or the inflammation of the membrane lining the joint, has never been analyzed using MRI-based structural biomarkers.”

Luitjens and her colleagues enrolled 277 people with moderate to severe osteoarthritis who used NSAIDs for at least one year, comparing them to a control group of 793 patients who were not treated with NSAIDs. All participants underwent an MRI of the knee at the start of the study and had another MRI four years later. 

The results showed no long-term benefits from NSAID use. The initial MRIs found joint inflammation and cartilage quality were worse in the participants taking NSAIDs, and their knee joints deteriorated even more after four years. 

“In this large group of participants, we were able to show that there were no protective mechanisms from NSAIDs in reducing inflammation or slowing down progression of osteoarthritis of the knee joint,” said Luitjens, who will present her findings next week at the annual meeting of the Radiological Society of North America (RSNA).

Luitjens says there are two possible reasons for the ineffectiveness of NSAIDs. One is that the anti-inflammatory effects of NSAIDs may not be sufficient to prevent synovitis. It’s also possible that patients with synovitis who use NSAIDs may be more physically active due to pain relief, which could have worsened their synovitis. 

In either case, Luitjens believes more evidence is needed to support the continued use of NSAIDs as a treatment for osteoarthritis.

“The use of NSAIDs for their anti-inflammatory function has been frequently propagated in patients with osteoarthritis in recent years and should be revisited, since a positive impact on joint inflammation could not be demonstrated,” she said.

The 2018 Krebs study did not look at how NSAIDs affected joint inflammation. It focused mainly on pain intensity, function and quality of life, and found few differences between opioids and NSAIDs, leading Krebs to conclude that opioids were “not superior” to NSAIDs. As my late colleague Roger Chriss pointed out, researchers also found no harmful effects in patients who took opioids for a year. There was no opioid misuse, addiction or overdoses — a detail rarely mentioned in news coverage of the study.

Osteoarthritis is a joint disorder that leads to thinning of cartilage and progressive joint damage. Knee osteoarthritis is quite common and affects over 250 million people worldwide. Nearly 40 percent of Americans over the age of 45 have some degree of knee osteoarthritis.