NSAIDs for Knee Osteoarthritis May Worsen Pain Over Time

CHICAGO — Taking nonsteroidal anti-inflammatory drugs (NSAIDs) for knee osteoarthritis (OA) may worsen inflammation and pain over time, suggest new data revealed at the Radiological Society of North America (RSNA) 2022 Annual Meeting.

Dr Johanna Luitjens

Johanna Luitjens, MD, a postdoctoral scholar in the Department of Radiology and Biomedical Imaging at the University of California, San Francisco, told Medscape Medical News that NSAIDs are frequently used to treat OA pain because inflammation is one of the main drivers of OA, but whether they actually help outcomes has been unclear. Her study suggests that they don’t help — and may actually worsen — outcomes.

In particular, this study looked at the impact of NSAIDs on synovitis — the inflammation of the membrane lining the knee joint — by using MRI-based structural biomarkers.

OA, the most common form of arthritis, affects more than 32 million adults in the United States and more than 500 million people worldwide.

No Approved Therapy to Reduce OA Progression

Little is known of the long-term effects of NSAIDs on OA progression. Currently, there’s no approved therapy to cure OA or to reduce its advance.

But, Luitjens noted that the synovial membrane mediates development and progression of OA and may be a good therapeutic target.

Researchers studied participants from the Osteoarthritis Initiative (OAI) cohort with moderate to severe OA who used NSAIDs regularly for at least 1 year between baseline and 4-year follow-up. All participants had high-quality 3T MRI of the knee at baseline and after 4 years. Images were scored for biomarkers of inflammation, including cartilage thickness and composition.

Luitjens and her team studied 721 participants who matched the inclusion criteria (129 with and 592 participants without regular NSAID use). The available data did not further specify amounts of NSAIDs used.

At baseline, significantly higher signal intensity in the infrapatellar fat pad (IFP) was seen in patients who used NSAID compared with controls (adjusted difference in score,  0.26; 95% CI [-0.5 to -0.129]; P = .039).

In addition, at the end of the study period, there was a significantly greater increase in signal intensity of IFP (0.46; [0.2-0.72]; P < .001) and higher increase in effusion synovitis (0.27; [0.06-0.47];  P = .01) in NSAID users compared with controls.

IFP size and synovial proliferation score (SPS) did not different significantly between groups at the start of the study and showed no significant change over time.

The results showed no long-term benefit of NSAID use. Joint inflammation and cartilage quality were worse at baseline in the participants taking NSAIDs compared with the control group and worsened at 4-year follow-up.

Design Limits Strength

Amanda E. Nelson, MD, Associate Professor of Medicine, Division of Rheumatology, Allergy, and Immunology in the Gillings School of Global Public Health in Chapel Hill, North Carolina, cautioned against assuming causality, pointing out that the OAI is an observational cohort study. (Dr Nelson was not involved in the OAI or Dr Luitjens’ analysis.)

Dr Amanda E. Nelson

“[The OAI is] large and well known, but it wasn’t designed to compare these groups, and this was a small subset,” she told Medscape Medical News. Without randomization, she said, it’s hard to judge the results.

“It may be that people on NSAIDs for the duration of the study had more pain and had more disease to begin with, or had more symptoms or had failed other treatments,” she said.

She also said the effect sizes were small.

Measures such as the IFP, she noted, are ranked 0-3, so “the clinical difference of a .26 difference on a 0-3 scale is a bit uncertain,” she said.

Luitjens said that the researchers tried to adjust for potential confounders but agreed that randomized controlled trials are needed to better advise physicians and patients on the benefits or harms of using NSAIDs for OA.

Weighing the Risks in Older Adults

Una Makris, MD, associate professor of internal medicine in the Division of Rheumatic Diseases and the School of Public Health at University of Texas Southwestern Medical Center​ in Dallas, noted that NSAIDs are “not always the safest option.”

Dr Una Makris

“We are still in desperate need of disease-modifying drugs in OA with rigorous randomized trials to show efficacy for outcomes that are most meaningful to patients,” Makris, who was not involved in the study, told Medscape Medical News.

“OA is most common in older adults, those often with multiple comorbidities, so we must always weigh the risks — including known adverse effects which can be amplified in older adults — and benefits with the goal of improved function and less pain,” Makris said.

NSAID use also should be considered in the context of body mass index, cardiovascular risk, prior trauma or injury, other medication use, and behavioral factors, including physical activity, she said.

Luitjens, Nelson, and Makris report no relevant financial relationships.

Radiological Society of North American (RSNA) 2022 Annual Meeting. Presented November 27, 2022. Abstract S3B SPMK

Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News, and Nurse.com, and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick

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