Severity of Local Skin Reactions with 4% 5-Fluorouracil Plus Emollient versus 4% 5-Fluorouracil Alone in Patients with Actinic Keratosis: A Single-Blind Randomised Trial

Abstract

Introduction: Topical 5-fluorouracil (5-FU)containing treatments are effective for actinic keratosis (AK); however, they frequently lead to transient local skin reactions (LSRs), which often result in treatment non-adherence. Methods: The aim of this international, phase IV clinical trial was to investigate whether addition of an emollient to topical 4% 5-FU would reduce the frequency and severity of LSRs over 4 weeks of treatment (intervention group) compared with 4% 5-FU alone (control group) in patients with AK. The primary objective was to assess the severity of LSRs (i.e. erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation and erosion/ulceration) at week 4 of treatment (or before, in case of a major local reaction). Key secondary objectives were LSR total scores at weeks 2 and 8, the scores of individual LSR items at each visit, and the proportions of patients with 100% and C 75% AK lesion clearance at week 8. Results: In total, 141 patients were included in the efficacy analysis (71 in the intervention group and 70 in the control group). There were no statistically or clinically significant differences between the treatment groups in terms of LSR total score at week 4 (overall and by subgroups defined by the number of lesions and patient age at baseline), scores of individual LSR items at any time point, and AK lesion clearance rates at week 8. LSR scores with topical 4% 5-FU alone were lower than expected. Skin reactions

Adherence to treatment in dermatology: Literature review

“…Retinoids (40%), benzoyl peroxide combinations (44.1%) and retinoid combos (60%) were the most often discontinued prescriptions, primarily due to side effects with reported rates of 50%, 33.3% and 65.7%, respectively 44 . Similarly, field‐directed topical 5‐fluorouracil‐containing treatments frequently lead to local skin reactions, such as erythema, scaling/dryness, flaking, oedema, crusting/scabbing, stinging/burning and pruritus, which increases treatment discontinuation 45,46 . Regarding oral acne medication, isotretinoin commonly causes skin dryness and erythema, which often limits adherence 47 .…”

“…44 Similarly, field-directed topical 5-fluorouracil-containing treatments frequently lead to local skin reactions, such as erythema, scaling/dryness, flaking, oedema, crusting/scabbing, stinging/burning and pruritus, which increases treatment discontinuation. 45,46 Regarding oral acne medication, isotretinoin commonly causes skin dryness and erythema, which often limits adherence. 47 In a study of 18 patients with advanced basal cell carcinomas, treatment fatigue due to adverse events, including muscle cramps, alopecia and dysgeusia, was the most common cause of discontinuation of vismodegib.…”

Tirbanibulin 1% Ointment for Actinic Keratosis: Results from a Real-Life Study

“…Local irritation remains the primary source of harm to patients and often the primary reason for the discontinuation of treatment, not influenced by the addition of emollient cream. The mean LSR total scores at week four showed no statistically significant differences between patients who received 4% 5-FU plus emollient and patients who received 4% 5-FU alone [19]. The 5-FU/SA cream has been evaluated for the treatment of slightly palpable and moderately thick hyperkeratotic AK lesions in a randomized controlled trial with a CCR of 49.5% reached eight weeks after the end of the twelve-week treatment.…”