Comparison of efficacy of topical diclofenac sodium 1% gel and acetaminophen extended-release for treatment of symptomatic knee osteoarthritis

Abstract Title: Comparison of efficacy of topical diclofenac sodium 1% gel and acetaminophen extended-release for treatment of symptomatic knee osteoarthritis

Background: Osteoarthritis (OA) affects over 32.5 million adults in the US.  Among primary care providers, two of the most recommended options to treat OA pain are the topical non-steroidal anti-inflammatory drug (NSAID) diclofenac sodium 1% gel (DSG) and acetaminophen. Current American College of Rheumatology (ACR) OA Guidelines strongly recommend DSG and conditionally recommend acetaminophen for treatment of knee OA.

Purpose/Objectives: The purpose of this analysis is to compare published clinical efficacy data of DSG to that of acetaminophen extended-release (AER) or sustained-release (ASR) for treatment of knee OA.

Method: A literature search through February 2023 (PubMed and EMBASE) screened for placebo-controlled clinical studies using the validated and well-known Western Ontario and McMaster Osteoarthritis Index (WOMAC) to evaluate treatment of symptomatic knee OA with either DSG or AER. Five 12-week studies were included in this review: two studies evaluating DSG (4g applied to 1-2 knees QID), two studies evaluating AER (1300 mg, TID), and one study evaluating acetaminophen sustained-release (2000 mg, BID). Each study had similar designs and patient demographics, and assessed WOMAC pain, physical function, and stiffness subscales at 12 weeks in patients with primarily knee OA.

Results: DSG and AER separated from placebo for the WOMAC endpoints in all studies, while ASR WOMAC scores did not separate from placebo. DSG demonstrated greater improvements from baseline than AER for each outcome.  DSG showed statistically significant decreases versus placebo in mean WOMAC pain (51-53%), function (47-50%) and stiffness (48-49%). AER groups demonstrated statistically significant decreases in mean WOMAC function (35-36%) and marginally to statistically significant decreases in mean WOMAC pain (38%, p=0.054; 38%, p=0.012) and stiffness (34%, p=0.004; 36%, p=0.088) versus placebo. Safety and tolerability of each treatment group were similar compared to respective controls.

Conclusions: In the studies evaluated, both DSG and AER demonstrated efficacy in WOMAC endpoints in patients with knee OA. Topical DSG treatment provided clinically significant improvements in pain, function and stiffness, which were noticeably greater than the results achieved with AER at nearly the maximum daily limit for acetaminophen. While AER may be an option for patients who cannot tolerate NSAIDS, these results should be considered by healthcare providers when recommending a treatment for knee OA.

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10. Data on file.