Clinical trials of diclofenac gel for actinic keratoses

The efficacy of 3% diclofenac hyaluronic acid (HA) gel (0.5 g applied twice daily to each 5 cm x 5 cm treatment area) in patients with actinic keratoses (AK) has been evaluated in at least 2 published randomised, double-blind, HA gel vehicle-controlled trials.

A multicenter, randomised, double-blind, placebo-controlled study treated 195 patients with diclofenac, 0.5 g or vehicle, twice daily for either 30 days or 60 days.

• Efficacy was assessed 30 days after the end of treatment because an earlier study revealed that resolution of lesions was greater when measured after a 4-week interval, rather than at the end of treatment.
• There was no statistical difference in complete responders in the 30-day treatment groups, but significantly more patients given active treatment for 60 days had target lesion number scores (TLNS)=0 (33% vs. 10%, p<0.05).
• With regard to cumulative lesion number scores (CLNS), 31% of patients in the active group showed complete clearance vs. 8% in the placebo group (p<0.05).

In a separate randomised, double-blind, placebo-controlled trial involving 117 evaluable patients, with >5 AK lesions, adult patients received either 3% diclofenac gel in 2.5% hyaluronan gel or the gel vehicle as a placebo. They received diclofenac 0.5 g twice daily for 90 days.

• Assessments were made at each visit and 1 month posttreatment, and included Target Lesion Number Score (TLNS), Cumulative Lesion Number Score (CLNS) and Global Improvement Indices (GII).
• At the follow-up visit, 50% of the patients using diclofenac showed complete resolution of all target lesions using TLNS compared to 20% in the placebo group (p<0.001). With regard to CLNS, 47% of patients applying diclofenac showed complete resolution compared to 19% in the placebo group (p<0.001) and the GII showed a 79% improvement in the diclofenac group vs. 45% in the placebo group (p<0.001).

A prospective, double-arm, multicenter, open-label, phase IV study performed at 82 community dermatology centres in the US and involving 521 evaluable patients has shown that the sequential treatment with cryosurgery followed by diclofenac sodium 3% gel for 90 days is well tolerated and can provide a more successful outcome than monotherapy with cryosurgery.

A separate multicentre, randomized open-label study including 418 patients with mild to moderate AKs has investigated whether prolonged treatment with diclofenac in HA for 6 months adds to the efficacy in treatment for AK.

• Complete lesion clearance was observed in 40% in group A (diclofenac in HA for 3 months) and in 45% in group B (diclofenac for 6 months; P = 0.38).
• Histopathological clearance was confirmed in 30% in group A and in 40% in group B (P = 0.16).
• Treatment was well tolerated and quality of life was significantly improved after treatment in both treatment groups.

Active comparator studies have demonstrated comparable efficacy of diclofenac sodium 3% gel with 5% 5-fluorouracil cream and 5% imiquimod cream.

In contrast to successful studies described above, a study in 130 patients did not show any statistical difference between topical 3% diclofenac in 2.5% hyaluronic acid (HA) gel (active) and a gel containing 2.5% HA alone (control) in the treatment of solar keratoses.