A multicentre pragmatic randomized controlled trial comparing 50% salicylic acid, liquid nitrogen, 5% 5-fluorouracil cream, and 5% imiquimod cream in previously treated plantar warts. The VRAIE (VeRrues plAntaIres en villE) study

Abstract

Background: Plantar warts are common among the general population. After failure of first-line treatment, they are challenging to treat.

Objectives: To compare 4 second-line treatments - 50 % salicylic acid ointment (SA) under occlusion, liquid nitrogen, 5 % 5-fluorouracil (5-FU) cream under occlusion, and 5 % imiquimod cream - in terms of complete remission after 90 days.

Methods: A multicentre, pragmatic, randomized, controlled trial. Screened patients with plantar warts were initially treated with a 5-week regimen of SA, followed by a 1-week washout period. Patients exhibiting treatment failure were randomly assigned to one of five treatments, with the allocation ratio fixed at 1:1:1:1:1. The fifth arm, treated with duct tape, was withdrawn during the study. We aimed to enrol 436 patients (109 in each treatment), but based on an anticipated response rate of 33 % in the pre-inclusion period, the target enrolment figure was increased to 660. An ancillary study (BIOVRAIE) was planned to analyse wart genotypes. The trial was registered on ClinicalTrials.gov (NCT01059110).

Results: A total of 358 patients (54 % of the target) were enrolled in the pre-inclusion period; 140 patients achieved complete remission during this period and 174 were included. Myrmecia warts constituted the most prevalent form of plantar warts (83.9 %), followed by mosaic warts (13.2 %) and a combination of both (2.8 %). Human papilloma virus (HPV) 27 and HPV1 infection were predominant (90 % and 84 %, respectively). At inclusion, 22 patients were assigned to the duct tape arm before its withdrawal, 41 to SA, 36 to cryotherapy, 33 to 5-FU, and 42 to imiquimod. On Day 90, 6 (20 %) patients in the SA group were in complete remission, as well as 3 (11 %) in the cryotherapy group, 1 (3.5 %) in the 5-FU group, 2 (6.6 %) in the imiquimod group.

Conclusions: While the trial failed to enrol the planned number of patients, the study showed that no treatment had a substantial positive effect as second-line treatment of plantar warts.

Keywords: Cutaneous warts; HPV; Topical treatment.