Conaghan PG, Dickson J, Bolten W et al. A multicentre, randomized, placebo- and active-controlled trial comparing the efficacy and safety of topical ketoprofen(Drug information on ketoprofen) in Transfersome gel (IDEA-033) with ketoprofen-free vehicle (TDT 064) and oral celecoxib(Drug information on celecoxib) for knee pain associated with osteoarthritis.
Rheumatology (2013) 52:1233-1238. doi:10.1093/rheumatology/kes434
A large randomized trial of two topical products for osteoarthritis (OA) available in Europe has found both of them as good as oral celecoxib in relieving knee pain over the course of three months.
The multicenter, double-blind controlled study randomized 1,395 patients with knee OA and moderate pain to one of six arms: 50 or 100 mg of the NSAID ketoprofen in a proprietary topical medium called IDEA-033, 2.2 or 4.4 g of another proprietary vehicle (TDT 064) that reportedly acts as a joint lubricant, 100 mg of oral celecoxib (the standard dose against OA), or a matching dose of oral placebo. The primary outcome was a change from baseline on the WOMAC pain subscale.
Manufacturers of both topical preparations are proposing them as safer alternatives to oral medications for osteoarthritis.
According to a press release by the manufacturer of TDT 064, which is a gel made of phospholipid vehicles, the preparation originally entered the trial as a second control for the effects of the vehicle. But it proved nearly as effective as the topical ointment that contained ketoprofen.
At week 12, the mean reductions in WOMAC scores were:
• 40.8% for ketoprofen 50 mg in IDEA-033
• 40.9% for ketoprofen 100 mg in IDEA-033
• 39.8% for 2.2 g TDT 064
• 37.8% for 4.4 g TDT 064
• 40.4% for oral celecoxib
• 29.3% for the oral placebo
The most frequent types of treatment-related adverse events were predictable: gastrointestinal for oral celecoxib (15.9%) and dermal for topical preparations (12.2% for ketoprofen 100 mg).
IDEA-033, manufactured by the Munich, Germany-based biotech IDEA, was created to address drug-delivery problems that have led to disappointment with topically administered NSAIDs for OA in the past. It contains so-called "transferosomes," ultra-deformable vesicles that can contain a drug. Applied epicutaneously (via shallow, blood-free needles as in the tuberculin test), the vesicles migrate through the skin but are too large to be trapped in the surface cutaneous microcirculation, as has happened with previous topical formulations.
A previous trial testing IDEA-033 only against celecoxib and oral placebo was published in the Annals of the Rheumatic Diseases in 2007, showing it equivalent to celecoxib in efficacy. Evidently the recent trial was intended to test the effect of inert vehicle, which proved nearly as potent against pain as the formulation under testing.
Marketed in Europe as Flexiseq by the Anglo-Russian firm ProBono Bio, the non-drug-containing topical gel TDT 064 is made of nanostructures called sequessomes. These vesicles are said to migrate through the skin to the joint, where they reportedly accumulate on damaged cartilage to form a lubricating layer.
Searches on the FDA website show no evidence of efforts as yet to obtain approval in the US.