Ketoprofen as good as diclofenac plasters for relieving aching knee

Topical ketoprofen and diclofenac yield comparable analgesic effects in the treatment of pain in patients with knee osteoarthritis (OA), with ketoprofen having a favourable safety profile, as shown in a phase III study.

Both ketoprofen and diclofenac produced marked improvements in knee pain intensity scores (measured on a 100-mm visual analogue scale) during walking at all time points, with the most significant effect seen after 3 weeks of treatment (mean change from baseline, −35.9 and −31.7 mm, respectively), according to the investigators.

Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are widely recommended in international guidelines as an early option for the symptomatic management of OA. And among topical NSAIDS, ketoprofen and diclofenac are the most commonly used. [Semin Arthritis Rheum 2019;49:337-350; Drugs Aging 2019;36:45-64; Osteoarthr Cartil 2019;27:1578-1589; Arthritis Care Res 2020;72:149-162]

When administered via a topical patch, ketoprofen and diclofenac can penetrate the subcutaneous or tissues, including the synovial tissue. This route of administration has been shown to produce higher drug concentrations in local synovial tissue as opposed to plasma concentrations following oral administration. [Curr Med Res Opin 2017;33:1623-1634; Clin Pharmacol Ther 2003;74:113-120; Arzneim Forsch 2002;52:822-827]

In the present study, 236 adults (average age 61 years, 79.6 percent female, body mass index 29.1 kg/m²) with OA-related knee pain were randomized to apply ketoprofen plaster 30 mg twice daily (n=118) or diclofenac plaster 15 mg once daily (n=118) for 3 weeks. Of these, 115 and 108 patients in the respective groups were included in the per-protocol analysis.

Results for the primary efficacy endpoint of mean knee pain intensity score during walking at the end of treatment confirmed the noninferiority of ketoprofen vs diclofenac (difference, −4.2 mm, 95 percent confidence interval, −9.6 to 1.1). Furthermore, the pain intensity score at rest after 2 and 3 weeks of treatment was much lower with ketoprofen (p<0.05). [Clin Ther 2021;doi:10.1016/j.clinthera.2021.08.002]

In terms of secondary endpoints, the mean Patient Global Impression of Improvement score showed a significantly greater increase with ketoprofen vs diclofenac after 2 and 3 weeks of treatment (p<0.001). On the other hand, the Knee Injury and Osteoarthritis Outcome Score improved with both drugs, with no statistically significant difference in terms of frequency of rescue medication use.

The overall adverse event (AE) profile of the groups was similar, with treatment compliance of 103 percent and 104 percent in the ketoprofen and diclofenac groups, respectively. There was no difference in skin reaction rates, including erythema or application site erythema (3.4 percent vs 5.1 percent), application site pruritus (0.8 percent in both groups), and application site hypersensitivity (0.8 percent vs 0 percent).

One huge advantage that topical NSAIDs bring in the treatment of OA of the knee is the reduced systemic exposure relative to oral NSAIDs, according to the investigators. “Topically applied NSAIDs [cut] the incidence of AEs typically associated with elevated systemic exposure to these agents when administered orally, such as gastrointestinal AEs.

“Moreover, topical NSAIDs are beneficial for patients who have comorbidities, difficulty swallowing oral medications (such as elderly patients), or who are otherwise intolerant to oral NSAIDs. It also minimizes toxic effects in patients with knee OA who are taking anticoagulants as well as those with renal and/or hepatic dysfunction, heart failure, or other comorbidities,” they continued.

Said to be the first to present results of a head-to-head comparison of ketoprofen and diclofenac plasters in patients with OA-related knee pain, the study is expected to aid in evidence-based clinical decision making, particularly with regard to initiation of topical therapy and switching from one product to another.

Nevertheless, the findings should be interpreted in light of the study limitations. The investigators acknowledged that there was no way to establish the assay sensitivity of the study because a placebo effect from the drug effect could not be delineated, and that the open-label trial design might have introduced potential response bias.