P-083 - (Poster #83) A prospective, real-world evidence study evaluating the effect of topical diclofenac (Voltaren gel) on functional mobility and quality of life in adults with osteoarthritis of the knee

Osteoarthritis (OA) is a leading cause of pain and disability worldwide.¹ Knee OA is characterized by progressive degeneration of articular structures, leading to chronic pain, joint stiffness and impaired mobility.² These symptoms compromise functional independence, disrupt sleep and reduce quality of life (QoL).³

The main goal in managing knee OA is symptom control, primarily pain relief and maintaining  joint function, through a combination of pharmacological and non-pharmacological strategies.^4,5 Among conservative pharmacologic treatments, topical nonsteroidal anti-inflammatory drugs (NSAIDs) are strongly recommended as first-line therapy, particularly for patients with localized symptoms or those at increased risk of systemic adverse events (AEs) from oral NSAIDs.^5,6
Topical diclofenac is a widely used topical NSAIDs for knee OA. It is indicated for the symptomatic relief of OA pain and has demonstrated statistically significant and clinically meaningful reductions in knee pain compared with placebo in randomized controlled trials (RCTs).^7-9 RCTs, while methodologically rigorous, may not reflect the complexity of real-world patient populations, adherence patterns and comorbidities. Real-world evidence (RWE) studies provide an opportunity to gather information on how treatments work in real-life scenarios and can potentially capture a broader range of patient behaviors and treatment outcomes than RCTs.

Purpose/Objectives:

While efficacy of topical diclofenac in knee OA is well established, understanding of the real-life impact of using topical diclofenac on functional mobility and QoL in patients with knee OA remains unexplored. 

This study aimed to evaluate the real-life effectiveness of topical diclofenac use in a representative population with mild to moderate OA of the knee, focusing on clinically relevant outcomes beyond pain relief. The outcomes investigated included the impact of topical diclofenac use on functional mobility, physical activity and other QoL parameters such as engagement in daily activities, sleep, and mood.

This study utilized a research-grade, validated actigraph device (ActiGraph^TM) to accurately and objectively measure changes in functional mobility, together with the use of clinically validated, comprehensive, subjective assessments to provide data on the real-world benefits of using topical diclofenac in patients with knee OA.

Methods:

This prospective, open-label, single-arm, RWE study, conducted at sites in Europe (EU) and the United States (US), enrolled adults aged 40–85 years diagnosed with mild to moderate knee OA and self-reporting pain at recruitment. Following baseline assessments, participants applied 1% diclofenac sodium gel (DSG 1%, US only), 1.16% diclofenac diethylammonium gel (DDG 1.16%, EU only) or 2.32% diclofenac diethylammonium gel (DDG 2.32%, EU only) daily per the label for up to 21 days. Participants wore an actigraph device throughout the study.
The primary endpoint was change from baseline in average minutes of moderate-to-vigorous physical activity (MVPA) at week 1 (days 1–7), week 2 (days 8–14) and week 3 (days 15–20) measured using actigraphy. Secondary endpoints measured using actigraphy included change from baseline at days 7, 14 and 21 in daily average number of steps, ratio of sedentary/non-sedentary time, gait speed and cadence, and indices of morning stiffness. Subjective endpoints, recorded daily using an eDiary, included Western Ontario and McMaster Universities Arthritis Index (WOMAC) subscale scores for physical function and pain, self-reported pain intensity using a numeric rating scale (NRS), sleep/alertness using the Karolinska Sleepiness Scale (KSS), health-related QoL using the EQ-5D-5L questionnaire, safety and product usage.

Results:

Overall, 196 adults were included (DSG 1%, n=39; DDG 1.16%, n=39 and DDG 2.32%, n=118). The mean (standard deviation [SD]) age was 61.8 (9.3) years; 60.2% were female. The mean (SD) duration of diclofenac treatment was 20.7 (1.2) days and overall mean (SD) study treatment compliance was 88.1% (14.3); these were similar across groups. Overall mean (SD) compliance with the actigraph device was 88.4% (13.8).

For the primary outcome, there was a significant improvement from baseline in average minutes of MVPA measured over the 3-week period (mean [SD] 8.5 [54.2], p=0.003). The mean (SD) change from baseline in average minutes of MVPA was 14.2 (53.5) at Week 1 (p< 0.001), 10.7 (60.9) at Week 2 (p=0.001) and -0.8 (71.1) at Week 3 (p=0.653).

Daily average number of steps taken increased from baseline at Week 1 (p< 0.001) and Week 2 (p=0.042), with Week 3 showing no significant change from baseline (p=0.670). Indices of morning stiffness showed inter-week improvements by Week 3 for both the 30-minute (p=0.013) and 60-minute (p=0.002) post-wake measures. An increase in the sedentary/non-sedentary time ratio was observed by Week 3 (p = 0.036) suggesting a relative increase in sedentary behavior. No significant changes were observed in gait speed or cadence across the observation period. Improvements were reported across all WOMAC domains: pain, stiffness, physical function and global score throughout the study period (p< 0.001, all time points), and NRS scores for pain decreased consistently (p< 0.001, all weeks). KSS scores showed improvement by Week 3 (p=0.002), suggesting delayed but meaningful improvement in daytime alertness. EQ-5D-5L scores were improved compared with baseline at each week (p< 0.001), indicating sustained improvement in health-related QoL. This composite measure encompasses physical function, pain, anxiety/depression and self-care. Topical diclofenac had a favorable safety profile with no serious AEs reported and all treatment-emergent AEs were mild to moderate.

These findings confirm the multidimensional symptom relief provided by topical diclofenac, consistent with RCTS showing that topical NSAIDs significantly improve OA-related symptoms¹⁰ which can have benefits across physical, emotional and social domains of health.¹¹

Conclusions/Implications for future research and/or clinical care:

This study combines objective data recorded using an actigraph device with patient reported outcomes collected from validated questionnaires to assess the therapeutic effects of topical diclofenac beyond pain relief.  It highlights improvements in mobility, reduced stiffness, enhanced daytime alertness, and better QoL.

The primary outcome, MVPA, is a key indicator of mobility, function and cardiometabolic health in people with OA. Early increases in MPVA suggest that topical diclofenac may rapidly relieve pain and stiffness associated with knee OA, promoting engagement in moderate intensity activities. This is significant for preserving joint range of motion and reducing comorbidity risk,^{12,13 with} even short-term gains potentially offering long-term health benefits.

A key strength of this study was the use of objective device-based measures of physical activity and stationary time, minimizing recall bias often associated with self‐reported activity measures. Additionally, the sample size and prospective design allow for robust examination of functional outcomes in a real-world setting. Study limitations include the single-arm design, potential confounding by the natural course of disease and short study duration.

Overall, this RWE study supports the use of topical diclofenac as a well-tolerated and effective first-line therapy for mild to moderate knee OA, improving pain, functional outcomes, and QoL.