Dose-finding Study: Topical Thalidomide for Aphthous Ulcers

Objective: We hypothesized that low dose topical administration of thalidomide would produce local tissue concentrations sufficient to promote ulcer healing without dose-limiting adverse effects.

Methods: We performed a double-blind, randomized, placebo-controlled dose-finding study of a novel topical thalidomide formulation for chronic oral aphthous ulcers in subjects with HIV/AIDS. Blood drawn serially was measured for thalidomide by HPLC using UV detection.

Results: A positive dose-response for healing was demonstrated in which 20 mg ointment exhibited an 87.5 percent probability of healing. The mean time to ulcer healing was 17 days for the 20 mg group versus 23 days for those healing in the placebo group. There were more unhealed ulcers (60 percent) in the placebo group compared to the other groups, resulting in a significantly greater percentage of subjects in the placebo group discontinuing topical treatment in favor of switching to thalidomide capsules. A dose response pattern was also observed for pain relief, with the most significant reduction observed for the 20 mg dose. There were no incidents of peripheral neuropathy, adverse events were similar between groups, and HIV plasma RNA levels did not change. The 20 mg dose was detectable in plasma 5 min post application and peaked at 1 hr. The remaining doses were below the level of reliable quantitation.

Conclusion: Topical thalidomide may be an effective alternative to PO thalidomide treatment for aphthous ulcers in patients with HIV infection, without the side effect liability.