Sjogren's syndrome
Randomized Controlled Trial of Diclofenac Sodium Gel in Knee Osteoarthritis

https://doi.org/10.1016/j.semarthrit.2009.09.002Get rights and content

Objectives

Nonsteroidal anti-inflammatory drugs have dose-related adverse effects. Topical nonsteroidal anti-inflammatory drugs may offer local efficacy with low systemic drug levels. This study assessed the efficacy and safety of topical diclofenac sodium 1% gel (DSG) in mild to moderate symptomatic knee osteoarthritis.

Methods

In a randomized, double-blind, vehicle-controlled trial, 492 adults aged ≥35 years with symptomatic knee osteoarthritis of ≥6 months' duration were randomized to DSG 4 g (n = 254) or vehicle (n = 238) 4 times daily for 12 weeks. Primary efficacy outcomes at week 12 were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, WOMAC physical function subscale, and global rating of disease. Secondary outcomes included these outcomes assessed after 1, 4, and 8 weeks, and pain on movement assessed using a 100-mm visual analog scale. All adverse events were recorded.

Results

At week 12, the DSG group had significant decreases versus the vehicle group in mean WOMAC pain (P = 0.01), mean WOMAC physical function (P = 0.001), and mean global rating of disease (P < 0.001). Efficacy outcomes significantly favored DSG versus vehicle beginning at week 1. Application site reactions occurred in 5.1% and 2.5% of patients in the DSG and vehicle groups, respectively. The incidence of gastrointestinal disorders was 5.9% with DSG and 5.0% with vehicle.

Conclusions

Over a 3-month treatment period, topical treatment with DSG achieved statistically and clinically significant improvements of pain and measures of physical function in patients with knee osteoarthritis.

Section snippets

Design Overview

This was a 12-week, randomized, double-blind, vehicle-controlled, parallel-group, multicenter trial. Following enrollment, eligible patients underwent a 1-week washout of analgesics (or at least 5 half-lives, whichever was longer) before being randomized to receive active drug or vehicle (placebo) daily for 12 consecutive weeks. Following the baseline visit, patients returned to the study site after 1, 4, 8, and 12 weeks for assessment of efficacy, safety, and compliance. Consistent with the

Patients

Of 492 randomized patients, 254 were assigned to receive DSG and 238 to receive vehicle; 82% and 75%, respectively, finished the study (Fig. 1). Demographic and baseline disease and symptom severity characteristics were similar in both groups (Table 2).

Efficacy

DSG was significantly superior to vehicle for all primary efficacy outcomes at week 12 (Fig. 2). Relative to baseline, patients treated with DSG exhibited greater mean decreases in WOMAC pain (−5.0 versus −4.0; P = 0.01), WOMAC function (−15.0

Discussion

In this 12-week trial, topical DSG was associated with significantly greater mean improvements versus vehicle in all primary efficacy outcome measures: the WOMAC pain subscale, WOMAC physical function subscale, and patient global rating of disease. Assessment of pain on movement, designated as an additional primary outcome for European regulatory purposes, also significantly favored DSG. Differences between DSG and vehicle were evident at week 1 and were maintained through week 12 on each

Acknowledgments

This study was funded by Novartis Consumer Health Inc, Parsippany, NJ. Funding of editorial support was provided by Endo Pharmaceuticals of Chadds Ford, PA. Employees of Novartis Consumer Health, Inc were involved in the study design, interpretation of results, and preparation of the manuscript. Selim A. Rachidi, MS (Novartis Consumer Health Inc), provided clinical operations support for the study. Jeffrey Coleman, MA (Complete Health Care Communications, Inc, Chadds Ford, PA), provided

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    This study was funded by Novartis Consumer Health, Parsippany, NJ. Funding of editorial support was provided by Endo Pharmaceuticals Inc, Chadds Ford, PA.

    Dr. Barthel, Dr. Longley, Dr. Haselwood, and Dr. Altman have no financial interests to disclose. Dr. Gold is an employee of Novartis Consumer Health, Parsippany, NJ.

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