What are the effects of topical Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)?

From the Guidelines

Topical NSAIDs are a recommended first-line treatment for localized musculoskeletal pain, offering effective pain relief with fewer systemic side effects compared to oral NSAIDs. The most recent and highest quality study, published in 2021 1, supports the use of topical NSAIDs, such as diclofenac, for managing osteoarthritis pain in the knee. This study found that topical diclofenac was superior to placebo and equivalent to oral diclofenac in reducing pain associated with OA of the knee.

Key benefits of topical NSAIDs include:

• Reduced risk of gastrointestinal adverse events compared to oral NSAIDs
• Effective pain relief for osteoarthritis of superficial joints, such as knees and hands
• Useful for acute soft tissue injuries, such as sprains and strains, and tendinopathies
• Particularly beneficial for elderly patients or those with contraindications to oral NSAIDs

Common topical NSAIDs include:

• Diclofenac (available as Voltaren gel 1%, applied 2-4g to affected area 4 times daily)
• Ketoprofen gel (5-10%, applied 2-3 times daily)
• Ibuprofen cream (5-10%, applied 3-4 times daily)

These medications should be applied to intact skin over the painful area with gentle massage until absorbed, typically for 1-2 weeks for acute conditions or intermittently for chronic conditions. However, they may cause mild skin irritation, rash, or photosensitivity in some users. The safety profile of topical diclofenac has been found to be consistent with results at 12 weeks, even at 1 year, as reported in a systematic review by Derry et al, cited in the 2021 study 1.

In terms of specific recommendations, the 2020 American College of Physicians and American Academy of Family Physicians clinical guideline 1 suggests that topical NSAIDs may be among the most effective interventions for pain reduction, improvement in function, and treatment satisfaction. The 2019 EULAR recommendations for the management of hand osteoarthritis 1 also recommend topical NSAIDs as a first-line pharmacological treatment due to their favorable safety profile and beneficial effects on pain and function.

Overall, topical NSAIDs are a safe and effective treatment option for localized musculoskeletal pain, and their use should be considered as a first-line treatment.

From the FDA Drug Label

The data described below reflect exposure to diclofenac sodium topical solution of 130 patients treated for 4 weeks (mean duration of 28 days) in one Phase 2 controlled trial. The most common adverse events with diclofenac sodium topical solution were application site skin reactions. These events were the most common reason for withdrawing from the study Application Site Reactions: In this controlled trial, application site reactions were characterized by one or more of the following: dryness (22%), exfoliation (7%), erythema (4%), pruritus (2%), pain (2%), induration (2%), rash (2%), and scabbing (<1%)

NSAIDs Topical

• The most common adverse events associated with diclofenac sodium topical solution were application site skin reactions.
• These reactions included dryness, exfoliation, erythema, pruritus, pain, induration, rash, and scabbing.
• The application site reactions were the most common reason for withdrawing from the study.
• It is essential to follow the instructions for use and apply the solution exactly as prescribed, at the lowest dose possible, and for the shortest time needed 2.
• Diclofenac sodium topical solution should only be used for the treatment of pain from osteoarthritis in the knee or knees 2.

From the Research

NSAIDs Topical Overview

• Topical NSAIDs are effective in providing pain relief for acute musculoskeletal conditions, such as sprains, strains, and overuse injuries, with minimal adverse events 3.
• Formulations of topical diclofenac, ibuprofen, ketoprofen, piroxicam, and indomethacin have demonstrated significantly higher rates of clinical success compared to matching topical placebo 3.
• Topical NSAIDs are recommended for non-low back, musculoskeletal injuries, and are considered a first-line treatment option for acute mild to moderate pain 4.

Efficacy of Topical NSAIDs

• Gel formulations of diclofenac, ibuprofen, and ketoprofen have been shown to provide the best effects, with diclofenac Emulgel having the lowest NNT of 1.8 (95% CI 1.5 to 2.1) for clinical success 3.
• Topical diclofenac sodium 1% gel has been approved for use in the United States and has demonstrated clinically meaningful analgesia in OA patients with a low incidence of systemic adverse events 5.
• Clinical trial data suggest that topical NSAIDs provide efficacy similar to oral NSAIDs, with far less systemic distribution, making them a safer option for patients with significant comorbidities 6.

Safety Profile of Topical NSAIDs

• Local skin reactions to topical NSAIDs are generally mild and transient, and do not differ from placebo 3.
• Systemic adverse events and withdrawals due to adverse events are rare, making topical NSAIDs a safer option compared to oral NSAIDs 3, 6.
• Topical NSAIDs have a lower risk of gastrointestinal, cardiovascular, and renal adverse events compared to oral NSAIDs, making them a preferred option for patients with a history of these conditions 4, 6.