A new technique for delivering an old nonsteroidal anti-inflammatory drug is just as effective as oral celecoxib for relieving the pain of knee osteoarthritis, German researchers report.
The NSAID ketoprofen, approved in both the United States and Europe, when combined in a gel that is capable of penetrating the skin directly to arthritic joints, was significantly better than placebo and comparable with celecoxib in relieving pain associated with an acute flare of knee osteoarthritis. Moreover, it did so without entering the systemic circulation, said Dr. Matthias Rother, head of research and development of IDEA AG, Munich, Germany, and colleagues.
The toxicities of systemic NSAID treatment are well known, and the newer COX-2 inhibitors are associated with elevated cardiovascular risks. Hence, the need for safer therapies, the investigators wrote.
The new technology, called Transfersome, is a special gel made up of nanoparticles too large to be absorbed into the microcirculatory barrier of the skin, Dr. Rother said in a telephone interview.
Numerous gel and cream NSAID preparations are available in Europe. All work by diffusion, with the drugs absorbed systemically when they are applied to the skin. But when an NSAID, in this case ketoprofen, is mixed with the nanoparticle gel, it is able to penetrate into deep muscle and joints and be released. The mixture of ketoprofen and Transfersomes is called IDEA-033, Dr. Rother said.
“Transfersomes are ultradeformable carriers loaded with an active substance and applied epicutaneously in an aqueous suspension. Once they are on the skin, the water in the suspension begins to evaporate, and this draws the carriers containing ketoprofen through the skin barrier to the specific target areas,” he explained.
To compare this form of ketoprofen delivery with celecoxib and placebo in the relief of knee OA, the investigators randomized patients for at least 6 months to either 110 mg epicutaneous ketoprofen in 4.8 g Transfersome plus oral placebo (138 patients), 100 mg oral celecoxib plus placebo gel (132 patients), or both placebo formulations (127 patients) twice a day for 6 weeks.
Efficacy was assessed by measuring the changes in the Western Ontario and McMaster Universities (WOMAC) Index of Osteoarthritis pain subscale, physical function subscale, and patient global assessment (PGA) of response from baseline to the end of the study, in the index knee.
Overall, the mean WOMAC pain subscale scores were reduced by 18.2 in patients who received IDEA-033, by 20.3 in patients who received celecoxib, and by 9.9 in those patients who received placebo.
The mean physical function subscale score was reduced by 14.6 in patients who received IDEA-033, 16.6 in those receiving celecoxib, and 10.2 in the placebo group.
The mean PGA of response scores were 1.8 in the IDEA-033 group, 1.7 in the celecoxib group, and 1.3 in the placebo group.
The differences in change between IDEA-033 and placebo were statistically significant for pain subscale (P = .0041) and PGA of response (P = .0015).
Gastrointestinal adverse events with IDEA-033 were similar to placebo, the investigators wrote. No GI bleeding occurred. The rate of nonserious GI adverse events for IDEA-033, at 9.4%, was similar to placebo and numerically lower than for celecoxib (13.6%).
One patient treated with celecoxib had a myocardial infarction, one patient treated with placebo had angina, and no serious cardiovascular events occurred in patients treated with IDEA-033.
The IDEA-033 patients had more erythema and more skin irritations than the group receiving placebo gel, the investigators added (ARD Online First, published online by the British Medical Journal on March 15, 2007, as 10.1136/ard.2006.065128).
Systemic exposure in the IDEA-033 group was between 1% and 5%, compared with that of celecoxib, Dr. Rother said.