Topical Diclofenac, an Efficacious Treatment for Osteoarthritis: A Narrative Review

Frédérique Bariguian Revel, Marina Fayet, Martina Hagen, Frédérique Bariguian Revel, Marina Fayet, Martina Hagen

Abstract

Multiple head-to-head trials have demonstrated that topical nonsteroidal anti-inflammatory drugs (NSAIDs), including topical diclofenac, provide at least equivalent analgesia, improvement in physical function, and reduction of stiffness compared with oral NSAIDs in osteoarthritis and have fewer systemic adverse events. While efficacy of topical diclofenac in osteoarthritis is well established, understanding of the time to onset of action, duration of effect, and the minimum effective concentration is limited. Factors likely to influence these parameters include drug penetration and localization. Diclofenac concentrations in the joint tissues are likely to be more relevant than plasma concentrations. However, although diclofenac penetrates and is retained in these "effect compartments" at the site of inflammation and drug activity, no specific minimum effective concentration of diclofenac in plasma or synovial tissue has been identified. Recent evidence suggests that a reduction in inflammatory markers may be a better predictor of efficacy than plasma concentrations. This narrative review explores existing evidence in these areas and identifies the gaps where further research is needed. Based on our findings, topical NSAIDs such as diclofenac should be considered as a guideline-supported, generally well-tolerated, and effective first-line treatment option for knee and hand OA, especially for older patients and those who have comorbid conditions and/or risk factors for various systemic (gastrointestinal, hepatic, renal, or cardiovascular) adverse events associated with oral NSAIDs, particularly at high doses and with long-term use.

Keywords: Anti-inflammatory agents; Arthralgia; Chronic pain; Diclofenac; Non-steroidal; Osteoarthritis.

Figures

Fig. 1
Fig. 1
NSAID modulation of COX-2 and NFκB pathways leads to decreases in PGE2 plasma levels and pro-inflammatory cytokines [–26]. COX-1 and COX-2, cycolooxygenase-1 and -2; EP2 and EP4, two of the four prostanoid receptors for prostaglandin E2; IL-1β, -6, and -8, interleukin-1β, -6, and -8; NF-кB, nuclear factor kappa B; NSAIDs, nonsteroidal anti-inflammatory drugs; TNFα, tumor necrosis factor alpha
Fig. 2
Fig. 2
Flow of diclofenac from topical application to the joint capsule showing known steps (green arrows) and potential influencers of minimum effective concentration (red question marks)

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