Trifarotene Cream is Effective for Acne-Induced PIH in Patients with Skin of Color

Post-inflammatory hyperpigmentation (PIH) is a prevalent and distressing sequela of acne, particularly in patients with skin of color, where treatment options remain limited. A poster presented at Maui Derm NP+PA Fall 2025 in Nashville, Tennessee, evaluates the efficacy and safety of trifarotene 50 μg/g cream in improving PIH and acne severity in a diverse patient population with moderate acne at risk for pigmentary sequelae.¹

Background

The incidence of PIH ranges between 45.5% and 87.2%.² One of the most frequently used therapies is topical retinoids, which have demonstrated a reduction in hyperpigmentation in patients with skin of color. In prior studies, topical trifarotene 0.01% showed significant anti-pigmenting properties in the SKH2 mouse.³ This research analyzed the efficacy and safety of trifarotene50 µg/g cream in patients with moderate acne at risk for PIH.

Methods & Materials

LEAP (NCT05089708) was a multicenter, randomized, double-blind, vehicle-controlled parallel-group study of male and female participants between the ages of 13 to 35. Each was diagnosed with moderate acne, defined as an Investigator’s Global Assessment (IGA) score of 3, as well as moderate-to-marked PIH on the face, defined as an overall disease severity (ODS) hyperpigmentation scale score between 4 and 6.

Patients had between ≥20 inflammatory lesions and ≥25 non-inflammatory lesions on the facial area. Additionally, participants with Fitzpatrick skin types between I to VI were included. Approximately 70% of the cohort were between IV and VI. Patients were randomized to receive either trifarotene 50μg/g (n = 60) or vehicle (n = 63). Along with the topical, patients were given a skin care regimen that included a gentle cleanser, moisturizer lotion, and oil-absorbing moisturizer with SPF 30.

To evaluate PIH at baseline and the conclusion of the study, investigators measured changes in PIH ODS score, post-acne hyperpigmentation index (PAHPI), and the size of PIH lesions. They also determined IGA success and photographed changes in the number of acne lesions. Tolerability and treatment-related adverse events were noted.

Results

At week 12, the absolute (−1.6 vs −1.1) and percent changes (−34.4 vs −23.6) in improvement in PIH ODS score were statistically significantly (p < 0.05) in the trifarotene group compared to vehicle. However, at week 24, which was the primary endpoint, the changes in both cohorts became comparable. According to post-hoc analysis, the percent change in PAHPI score (size, intensity, and number) at week 24 was –18.9% in the trifarotene arm and –11.3% in the vehicle arm (p < 0.001). Furthermore, throughout the trial, photographic evidence showed visual improvements in hyperpigmentation across all skin types.

The mean percentage reduction in acne lesions was much higher in trifarotene-treated patients than in vehicle-treated patients, both at week 12 (–64.1% vs –46.7%, p < 0.001) and week 24 (–72.0% vs –62.8%, p < 0.05). Similar trends in the IGA success levels were seen in the trifarotene group at both time points.

Regarding trifarotene’s safety profile, those using the topical were more prone to experiencing signs of local tolerability like erythema, dryness, scaling, and stinging/burning, at weeks 1 and 2. These declined throughout the trial. Treatment-emergent adverse events were more prominent in the vehicle group (30.2%) than in the trifarotene group (16.7%). The most frequent adverse effects in the trifarotene cohort were COVID-19, influenza, nasopharyngitis, vomiting, attention deficit hyperactivity disorder, oropharyngeal pain, and muscle spasms. These were mild to moderate in nature and not related to the study drug.

Conclusion

At both weeks 12 and week 24, patients treated with trifarotene observed improvements in PIH clearance, PAHPI score, and IGA acne success. Overall, trifarotene 50 μg/g cream was well-tolerated in all skin types, making it a suitable therapy for patients with acne-induced PIH.

References

1. Alexis A, Cesljarevic E, Browning J. Efficacy and safety of trifarotene cream 50 µg/g for the treatment of acne-induced post-inflammatory hyperpigmentation in subjects with Fitzpatrick Skin Types I–VI: Results from a phase IV trial (LEAP). Poster presented at Maui Derm NP+PA Fall 2025, September 20-23, Nashville, Tennessee.

2. Schuster B, et al. Less confident, successful and happy: patients with post-acne hyperpigmentation are stigmatized. Br J Dermatol. 2023;188(5):682-684

3. Aubert J, et al. Nonclinical and human pharmacology of the potent and selectivetopicalretinoicacidreceptor-γ agonist trifarotene. Br J Dermatol. 2018;179(2):442-456.