Patient Insights on Acne Hyperpigmentation, Trifarotene, and Skincare: 6-Month, LEAP Phase 4 Qualitative Exit Interview Findings

Abstract

Background

Acne-induced hyperpigmentation (AIH) has a considerable impact on patients’ quality of life (QoL). In the phase 4 LEAP trial, patients treated with the topical retinoid trifarotene showed faster improvement in AIH compared to patients treated with its vehicle cream (VC) at week (W) 12.

Objective and Methods

This was a cross-sectional, blinded, qualitative interview study embedded in the phase 4 LEAP trial (NCT05089708), which assessed the safety and efficacy of trifarotene (50 μg/g) versus its VC in the treatment of acne. The study was conducted with a subsample of participants between June and November 2022 at a subset of nine clinical sites in the United States (US). Participants were adults (18–34 years) who were randomized to receive trifarotene (50 μg/g) or VC, along with a daily skincare regimen (moisturizer, cleanser, photoprotection). After confirming participants’ end-of-treatment visit during W24, telephone interviews were conducted using a semi-structured interview guide. Participants’ perspectives regarding baseline AIH symptoms, changes in AIH from baseline to W24, and treatment satisfaction were assessed and analyzed using thematic analysis in ATLAS.ti to better understand trends across trial arms.

Results

Thirty participants (n = 12 in the trifarotene group and n = 18 in the VC group) (mean [standard deviation {SD}] age, 24.8 [4.7] years; 80.0% male) were interviewed. At W24, more participants in the trifarotene group (100%) than the VC group (83.3%) reported an improvement in AIH and that the change was meaningful (91.7 and 83.3%, respectively). AIH severity change (mean [SD]) from baseline to W24 was higher in the trifarotene group (−5.5 [2.5]) than the VC group (−3.5 [2.1]). More participants in the trifarotene group (≥ 90%) than in the VC group (≥ 73%) reported a meaningful improvement in their emotional functioning, personal care/hygiene, and social life/relationships. Treatment satisfaction was higher in the trifarotene group (mean [SD] = 8.6 [2.1]) than in the VC group (mean [SD] = 7.6 [3.1]).

Conclusion

All trifarotene-treated patients reported improvements in AIH and that their treatment expectations were met. Findings support that trifarotene plus a skincare regimen provides greater benefit in the improvement of AIH than its VC. However, VC plus a skincare regimen also appeared to improve patients’ perceptions of their AIH.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40271-025-00789-9.

Key Points for Decision Makers

This optional qualitative exit interview study of 30 adults with moderate acne focused on patients’ perspectives regarding the effect of trifarotene treatment plus a skincare regime on acne-induced hyperpigmentation (AIH) and quality of life.

More participants treated with trifarotene plus a skincare regime than those treated with its vehicle cream plus a skincare regime reported a decrease in AIH severity, meaningful improvements in AIH and quality of life, and high treatment satisfaction.

The patient-perceived benefit of trifarotene plus a skincare regime for the treatment of AIH supports previous data demonstrating the safety and efficacy of trifarotene.

Introduction

Acne vulgaris affects approximately 9.4% of the global population [1]. In adults, acne presents as comedones (blackheads, whiteheads), papules, pustules, nodules, cysts, or lesions on the face, chest, and back [2]. Patients with acne also experience acne-induced hyperpigmentation (AIH) (i.e., an area of darker skin caused by inflammation-induced excess melanin production that may persist after the acne lesion has healed), resulting in excess melanin production [3]. AIH occurs in 45.5–87.2% of patients with acne, is influenced by skin phototype (Fitzpatrick skin type), and takes over a year to fade [4]. Acne and AIH have a considerable impact on patients’ quality of life (QoL), including physical health, self-esteem, depression, social avoidance, interpersonal relationships, productivity and absenteeism, stigmatization, and treatment concerns [4–8]. Effective acne treatments, use of sunscreen, and sun avoidance measures are recommended for AIH management [9].

Topical retinoids are commonly used to treat acne and have shown substantial anti-inflammatory effects that mitigate symptoms such as redness, swelling, and discomfort [10, 11]; however, they can cause irritation, dry skin, erythema, and peeling [12]. Topical retinoids are incorporated in vehicle creams (VCs) (inactive creams, lotions, or ointments) to increase the tolerability and facilitate absorption of topical retinoids [13, 14].

Trifarotene is a topical retinoid cream that selectively targets the retinoic acid receptor gamma in the skin [15, 16]. Trifarotene has been approved by the United States (US) Food and Drug Administration for the treatment of acne in patients aged ≥ 9 years [15, 17]. In two 12-week phase 3 studies of trifarotene (50 µg/g) versus its VC (NCT025566369 and NCT02556788), patients treated with trifarotene had higher Investigator’s Global Assessment scores for the resolution of face lesions and improvements in noninflammatory and inflammatory lesion counts than patients treated with VC [15]. In a phase 4 study evaluating the effect of trifarotene on facial acne and atrophic scars in patients with moderate to severe facial acne (NCT04856904), at week 24, there was a greater reduction in the mean absolute change from baseline in total atrophic scar count in trifarotene- versus vehicle-treated skin areas (p < 0.0001) [18]. In the phase 4 LEAP study evaluating the safety and efficacy of trifarotene (50 μg/g) versus its VC (NCT05089708), patients treated with trifarotene showed rapid and significant improvements in AIH compared with patients treated with VC after 12 weeks [9]. In the phase 4 LEAP study, patients treated with trifarotene showed a rapid and significant decrease in overall disease severity, compared with patients treated with VC, at week 12 (p = 0.03) [9]. Patients treated with trifarotene also had a greater reduction in post-acne vulgaris hyperpigmentation index score at week 24 (p < 0.01) [9].

Qualitative data from exit interviews can provide details on patient perspectives that cannot be captured using patient-reported outcome (PRO) instruments and can help incorporate the patient’s voice into the drug development process [19, 20]. Understanding patients’ experiences with AIH and changes in AIH that are meaningful to them can help inform treatment decisions. We conducted exit interviews with a subset of participants enrolled in the LEAP trial to gain insight into their experience with acne and AIH before and during the trial, as well as their treatment experience and satisfaction.

Methods

Study Design

This was a cross-sectional, blinded, qualitative exit interview sub-study embedded in the phase 4 LEAP trial evaluating the efficacy and safety of trifarotene (50 μg/g) versus its VC in the treatment of acne with risk of AIH (NCT05089708). The study was conducted between June and November 2022 at nine clinical sites in the US, including two sites in Louisiana, two sites in Texas, and one site each in California, Florida, Indiana, New York, and Oklahoma.

The LEAP trial consisted of a 24-week treatment period, in which participants (N = 123) were randomized (1:1) to receive daily trifarotene (50 μg/g) or its VC (patients received the VC that is incorporated into trifarotene). Participants were also provided skincare products (cleanser, moisturizer, photoprotection) to use in tandem with study treatment. Patients in the LEAP trial were invited to participate in the exit interview sub-study and informed that enrollment in this study was optional. The exit interviews were conducted with a subset of LEAP trial participants (N = 30) between week 24 and week 26 after confirming their end-of-treatment visit. Interviewers and participants were blinded to treatment at the time of the interview. The study protocol was approved by an institutional review board and ethics committee (Advarra IRB, US [RD.06.SPR.204245/260919] and the Comité de Ética de la Investigación con Medicamentos Hospital General Universitario Gregorio Marañón, Spain [Minutes No. 23/2021]). All participants provided written informed consent.

Study Population

Participants were adults (18–34 years) with a clinical diagnosis of acne vulgaris and Fitzpatrick skin types I–VI who had participated in the LEAP trial. Participants had to have completed their week 24 visit and were excluded if they had discontinued treatment or withdrew from the trial early. Eligibility criteria for the LEAP trial are described in the “Supplemental Methods” (see the electronic supplementary material).

Data Collection

All interviews were conducted using a semi-structured interview guide by interviewers (NT, TF, CR) trained in qualitative research methods. Telephone interviews (~ 90 min) were conducted in English and were audio-recorded and transcribed. The interview guide focused on participants’ experience of AIH before the trial and expectations of the trial; changes in AIH during the trial; and overall perception of the treatment during the trial (eTable 1; see the electronic supplementary material).

Participants were asked by the interviewer to rate the severity of their AIH at baseline and week 24 on a 11-point scale (0 =  “least severe” and 10 =  “most severe”). Participants rated the improvement of AIH in the clinical trial using a 5-point global assessment of change scale (“much worse,” “a little worse,” “no change,” “a little better,” or “much better”) and whether the change (improvement or worsening) was meaningful to them. Participants also rated their satisfaction with the treatment during the interview on a scale of 0–10 (0 = “not satisfied at all” and 10 =  “extremely satisfied”). Sociodemographic and clinical data collected during the LEAP trial were used to characterize the exit interview sample. PRO scores (AIH overall disease severity at baseline and week 24) were extracted from the PRO data collected in the LEAP trial.

Data Analysis

A mixed methods approach was used in this study, which involved integrating quantitative data from the LEAP trial to describe the study sample and contextualize findings from the qualitative study [21, 22].

Quantitative data from the LEAP trial included participants’ sociodemographic and clinical characteristics as well as data from PROs. Quantitative data were summarized using descriptive statistics.

Interview transcripts were analyzed using ATLAS.ti version 22 by four coders who were trained in the use of the study-specific coding dictionary, two of whom also served as interviewers. Qualitative data obtained during the interviews were reviewed, and key themes raised by participants were identified. Subgroup analyses were conducted to explore potential differences in participants’ experiences, perceptions, and outcomes across the treatment and control groups. A thematic analysis was conducted on blinded data from the exit interviews. After unblinding of the clinical trial database, exit interview data were organized in subgroups to identify treatment-specific patterns and insights to ensure that the qualitative findings were meaningfully interpreted within the framework of the randomized trial. A coding dictionary was developed based on the interview guide and on themes and concepts that emerged during the interviews. Saturation analysis was performed to determine when no substantially new concepts of interest were being identified during interviews [23, 24]. Briefly, transcripts were ordered chronologically (based on interview completion date) and grouped into sets of six interviews per group (i.e., five interview groups in total) (eFigure 1; see the electronic supplementary material). Concepts occurring in each group were collected and compared with those in the previous group to identify new concepts. Saturation was deemed to have been achieved when no new concepts of interest emerged in an interview group, indicating that additional interviews were unlikely to yield new patient insights.

Results

Participants’ Characteristics

Thirty patients participated in this study (n = 12 in the trifarotene group and n = 18 in the VC group) (Table 1). Sociodemographic characteristics of participants from the exit interview and clinical trial were comparable. Participants’ mean (standard deviation [SD]) age was 24.8 (4.7) years. Most were male (n = 24/30, 80.0%) and non-Hispanic/Latino (n = 22/30, 73.3%). Half of the participants were Black/African American (n = 15/30, 50.0%). Participants presented with the Fitzpatrick skin types II–VI (Table 2).

Table 1.

Participant demographics

	Exit interview N = 30	Clinical triala N = 123
Age
Mean (SD)	24.8 (4.7)	22.3 (6.1)
Min, max	(18, 34)	(13, 35)
Sex, n (%)
Female	6 (20.0)	30 (24.4)
Male	24 (80.0)	93 (75.6)
Race, n (%)
American Indiana/Alaskan Native	1 (3.3)	1 (0.8)
White	9 (30.0)	56 (45.5)
Black/African American	15 (50.0)	45 (36.6)
Asian	4 (13.3)	17 (13.8)
Native Hawaiian/other Pacific Islander	0 (0.0)	2 (1.6)
Other	1 (3.3)	2 (1.6)
Ethnicity, n (%)
Hispanic/Latino	8 (26.7)	48 (39.0)
Not Hispanic/Latino	22 (73.3)	75 (61.0)

SD standard deviation

^aPhase 4 LEAP trial (trifarotene 50 μg/g vs its vehicle cream; NCT05089708)

Table 2.

Participants’ experiences with AIH before trial

	Total N = 30
Years experiencing acne symptoms, n (%)
< 5	5 (16.7)
5–10	10 (33.3)
11–15	9 (30.0)
16–20	2 (6.7)
Did not reporta	4 (13.3)
Fitzpatrick skin type, n (%)
Type I	0 (0.0)
Type II	4 (13.3)
Type III	4 (13.3)
Type IV	6 (20.0)
Type V	9 (30.0)
Type VI	7 (23.3)
Treatment assignment, n (%)
Trifarotene	12 (40.0)
Vehicle cream	18 (60.0)
Able to distinguish between acne symptoms, AIH, and erythema, n (%)b
Yes	25 (83.3)
No	5 (16.7)
Terms used to describe AIH, n (%)
Dark spots	13 (43.3)
Hyperpigmentation	9 (30.0)
Acne scars	6 (20.0)
Family history of acne and/or AIH, n/N (%)c	18 (64.3)
Location of AIH, n (%)
Cheeks	17 (56.7)
Chin	8 (26.7)
Forehead	7 (23.3)
AIH triggers, n (%)d
Sun exposure	9 (37.5)
Makeup/skincare products	9 (37.5)
Diet	7 (29.2)
Stress	6 (25.0)
Impact of AIH, n (%)
Emotional functioning	28 (93.3)
Personal care/hygiene	24 (80.0)
Social activities/relationships with otherse	21 (72.4)
Financial burden	12 (40.0)
Impact on daily activities	4 (13.3)
Impact on sleep	1 (3.3)
Previous treatments, n (%)
OTC products and home remedies	26 (86.7)
Prescription treatments	7 (23.3)
Corrective procedures	3 (10.0)
Treatment expectations for the trial, n (%)e
Improvement of AIH or acne symptoms	14 (48.3)
Excitement	1 (3.4)
No expectations	14 (48.3)
Hope for change in AIH, n (%)
Have dark spots disappear	10 (33.3)
Lighten areas of AIH	5 (16.7)
Help skin condition in general	4 (13.3)
Prevent more AIH spots from forming by preventing acne	3 (10.0)
Even out skin tone	3 (10.0)
Reduce hyperpigmentation as well as acne	3 (10.0)
Make bumps go away	1 (3.3)
No hopes for change in AIH	1 (3.3)
Hope for change in AIH impacts, n (%)c
Emotional functioning	13 (46.4)
Social life/relationships with others	6 (21.4)
Personal care/hygiene	4 (14.3)
Daily life	3 (10.7)
No hopes for change in AIH impacts	2 (7.1)

AIH acne-induced hyperpigmentation, OTC over-the-counter

^aThese participants recalled that they had been experiencing acne symptoms since the time they were teenagers

^bAcne symptoms include blackheads, whiteheads, papules, pustules, nodules, and cysts. AIH is a flat area of darker skin where acne has healed [3, 27]. The discoloration observed in AIH is due to excess melanin produced as part of the skin's response to inflammation. AIH can appear white, pink, red, purple, brown, or black, depending on the patient’s skin tone and the depth of the discoloration. Post-inflammatory erythema is residual erythema after acne has resolved

^c28 respondents

^d24 respondents

^e29 respondents

Data Saturation

Twenty-four impact concepts were expressed by participants during the interviews conducted across five groups (six interviews per group) (eTable 2; see the electronic supplementary material). Most of the AIH impact concepts (n = 15, 62.5%) emerged during group 1 interviews: five concepts in emotional impacts, two in personal care/hygiene, six in social activities/relationships with others, one in financial impact, and one in daily activities. No new concepts appeared in the fifth group, indicating that concept saturation was achieved in the fourth group (corresponding to the 24th interview).

Participants’ Experience of AIH Before the Trial

Sixty-three percent of the participants reported experiencing acne symptoms for 5–15 years (n = 19/30) (Table 2). Most were able to distinguish between symptoms of acne and AIH (n = 25/30, 83.3%). Participants described their AIH as “dark spots” (n = 13/30, 43.3%), “hyperpigmentation” (n = 9/30, 30.0%), or “acne scars” (n = 6/30, 20.0%) that occurred on their cheeks (n = 17/30, 56.7%), chin (n = 8/30, 26.7%), or forehead” (n = 7/30, 23.3%).

“Some of them were so big it was kind of hard to tell them apart from each other. It felt like they were overlapping, they were bunched up to the point where unless you looked directly in my eye area like I was saying, you wouldn’t be able to tell my skin was not that color” (trifarotene group).

“The hyperpigmentation is much darker than my skin…it makes my skin look uneven. It looks splotchy, like something is wrong…is what it is, the dark spots” (VC group).

Twenty-four participants reported makeup or skincare products (n = 9/24, 37.5%), sun exposure (n = 9/24, 37.5%), diet (n = 7/24, 29.2%), and stress (n = 6/24, 25.0%) as the main triggers for AIH.

“Yes, my diet and stress. Stress causes me to pick at them. But definitely diet…if I drank sodas or eat too much chocolate my face breaks out worse and then I’m picking at it” (VC group).

Most reported using over-the-counter medicines/home remedies to treat AIH symptoms (n = 26/30, 86.7%). The mean (SD) severity rating for AIH before the trial was 6.9 (2.0) and was slightly higher among participants with Fitzpatrick skin types V (7.7 [1.8]) and III (7.6 [1.1]).

Participants reported that AIH had negative impacts on their QoL, including their emotions (n = 28/30, 93.3%), personal care/hygiene (n = 24/30, 80.0%), and social activities or relationships with others (n = 21/29, 72.4%) before the trial (Table 2).

“Embarrassing. It’s so embarrassing…self-conscious, insecure…when I would go meet friends or…hang out with people…I feel like my whole face is so bad” (trifarotene group).

“Yeah, because I used…so many different products trying to make my face look better, feel better, you know? And it wasn’t working, I’d give so much money, so much time doing different routines... Watching people’s YouTube accounts…try to use the same things they did, that made their face look good and it wasn’t working for me” (VC group).

“We live in a world where…there is social pressures to look a certain way…I think I have pretty high standards for my physical looks…it just felt like it was the one thing out of my control. I can control how skinny I am and how fit I am and all these other things, and it was like this is something that everyone sees. Our faces are one of the main things people look at” (trifarotene group).

One participant reported not experiencing any QoL impacts related to AIH before the trial (3.3%). The mean (SD) disturbance rating for AIH before the trial was 6.5 (2.9) and was slightly higher among participants with Fitzpatrick skin types V (7.9 [2.0]) and VI (7.5 [2.3]).

Forty-eight percent of the participants reported that a decrease in acne symptoms or AIH (n = 14/29, 48.3%) was their main treatment expectation in the trial (Table 2). Participants reported that their hope for change in AIH or AIH-related impacts included having dark spots disappear (n = 10/30, 33.3%), better emotional functioning (more self-confidence or less anxiety/helplessness) (n = 13/28, 46.4%), and improvement in their social life/relationships (more courage to talk to people) (n = 6/28, 21.4%).

“I was hoping that the cream would work. I didn’t have expectations that it would, because a lot of products I tried didn’t” (trifarotene group).

“Just hoping that this ointment would work for me and that I could just feel better, look better, go about the world happily instead of sad because I’m not looking like my best self. And yeah, just boosting confidence, I guess, to sum it up. Boosting my confidence” (VC group).

Changes in AIH During the Trial

Changes in AIH by Treatment Group

Twenty-seven participants (90.0%) reported an improvement in AIH during the trial (n = 12/12, 100.0% in the trifarotene and n = 15/18, 83.3% in the VC group) (eFigure 2; see the electronic supplementary material). Two VC group participants reported experiencing no change (11.1%), and one reported worsening in hyperpigmentation (5.6%). Of the 28 participants who observed a change in AIH (improvement or worsening), 12 (42.9%) reported perceiving a change between 4 and 8 weeks after starting the trial (n = 5 in the trifarotene group and n = 7 in the VC group).

Most participants who described a decrease in AIH (n = 27/30, 90.0%) also reported that the discoloration due to AIH was “fading” and that their skin appeared “lighter” or “brighter” (n = 24/27, 88.9%). A similar proportion in both treatment groups reported that areas of hyperpigmentation seemed to “go away” or were “disappearing” (n = 11/27, 40.7%). Forty-one percent reported a decrease in the size or coverage of areas with hyperpigmentation (n = 11/27), an improvement described by twice as many recipients of VC (n = 8/15, 53.3%) as trifarotene (n = 3/12, 25.0%). Some reported that the texture of their skin had improved during the trial (n = 3/27, 11.1%).

“Yes, like 100 percent. I have noticed a…decrease in hyperpigmentation... Like way more even skin tone, lighter, my skin got brighter, lighter, the dark spots have faded” (trifarotene group).

“I don’t think I have any dark marks on my forehead at all. I might have one, but as far as how it used to be, none on my forehead. If they are not completely eradicated, they’re super light now. Same for on my cheeks, most of them are just a lot lighter” (trifarotene group).

“Yeah…my face felt smooth and when I go outside, the wind just feel cool and nice, just feel refined” (VC group).

In the VC group, one participant (3.3%) reported worsening in AIH due to an increase in the number of hyperpigmented areas on their face. Two participants (6.7%) in the VC group who reported no change in AIH described a worsening of their exacerbation of acne symptoms (scars, blackheads).

“I definitely have more, unfortunately” (VC group).

“To me I didn’t really see a difference… The doctor did…he can see it better than I can. I noticed there was a big difference in the black heads and white heads and that sort of thing, but as far as the scars, it looked the same to me” (VC group).

Meaningful Change in AIH by Treatment Group

All trifarotene-treated participants reported improvement (n = 12/12, 100.0%) and rated their change as “much better” (n = 10/12, 83.3%) or a “little better” (n = 2/12, 16.7%), with most reporting that the change was meaningful (n = 11/12, 91.7%) (eTable 3; see the electronic supplementary material). One participant who reported a “little better” AIH said the change was not meaningful. Among participants in the VC group who reported an improvement in AIH (n = 16/18, 88.9%), 11 rated the change as “much better” (61.1%) and four rated the change as a “little better” (22.2%). A participant who reported worsening said the change was a “little worse” (5.6%).

“It’s extremely meaningful. I sat in shock for like about five minutes when I first saw the comparison pictures… I was very emotional that first time I saw my face, because I was like, I can enjoy life now because I’m not worried about what my face looks like” (trifarotene group).

“It helps me feel better about myself. I would say it improved psychological well-being” (VC group).

Change in Severity of AIH from Baseline to Week 24

Both treatment groups showed a decrease in AIH severity from baseline to week 24 (Fig. 1). The mean change in severity of AIH declined (improvement) from baseline to week 24 by 5.5 points in the trifarotene group and by 3.5 points in the VC group.

Fig. 1.

Change in AIH severity from baseline to W24. AIH severity ratings were assessed during participant interviews at baseline and W24 (based on retrospective recall) using a 0–10 scale (0 = “least severe” and 10 = “most severe”). AIH acne-induced hyperpigmentation, SD standard deviation, W24 week 24

Change in AIH Impacts During the Trial

All participants in the trifarotene group (n = 11/11, 100.0%) and most from the VC group (n = 14/17, 82.4%) reported an improvement in emotional functioning during the trial (eFigure 3; see the electronic supplementary material). Two participants from the VC group reported no change (11.8%), and one reported worsening (5.9%) in emotional functioning.

“A little better…because I feel more confident in my skin in to go outside, and I guess overall, I am buying less makeup, which is better for my finance” (VC group).

“I’m going to say much better. It’s an important improvement, because my face is just much better than before. I was really upset before with my face. It was crazy. And now everything changed” (trifarotene group).

“It increases my self-confidence. It cuts down on my daily routine, now I don’t have to put in as much effort trying to cover it up. I feel like I am just more comfortable meeting new people…easier and more comfortable” (trifarotene group).

Participants in the trifarotene group (n = 10/11, 90.9%) and the VC group (n = 11/13, 84.6%) reported improvements in personal care/hygiene. One participant from the trifarotene group reported no change (9.1%), and one from the VC group reported a worsening (7.7%) in personal care/hygiene.

“It’s much better. Yes, [that is meaningful to me]…if I were to put on makeup, it wouldn’t take like a whole thick layer to cover my dark spots... It really just helps my self-confidence, again, and helps me feel less helpless and not so frustrated” (trifarotene group).

“Much better…[it is meaningful]. I can get more done in the mornings. I have my son, I got to get ready for school and all kind of stuff. So, I really don’t have that hour to spend on my face” (VC group).

Most participants from the trifarotene group (n = 9/10, 90.0%) and VC group (n = 8/11, 72.7%) reported improvements in social activity/relationships, whereas one participant from the trifarotene group (10.0%) and three from the VC group (27.3%) reported no change.

“Much better… Yes, [it is meaningful] because I do want to genuinely…spend time with people. So, to be able to go out and spend time with people I love and care about and be free and have genuine fun without worrying whether or not they’re staring at the sight of my face, is a really good feeling” (trifarotene group).

“Yes, [this change was meaningful to me]…it just overall helped me help my lifestyle a lot more because I was feeling more confident about myself. And it allowed me to go out and socialize and be somewhat comfortable” (trifarotene group).

All changes (improvement or worsening) in emotional functioning, personal care/hygiene, and social activities/relationships were perceived as meaningful by participants. The mean AIH disturbance rating declined (improvement) from baseline to week 24 by 4.5 points in the trifarotene group and 3.7 points in the VC group (eTable 4).

Patients’ Perception of Treatment Experience

Treatment characteristics most liked by participants included treatment administration (n = 21/30, 70.0%), ease of use (n = 18/30, 60.0%), treatment effectiveness (n = 16/30, 53.3%), and time of effect (n = 11/30, 36.7%) (eTable 5; see the electronic supplementary material).

“The texture of it was really nice… I liked how it felt on my face. I like that it was easy to go in my skin. And it wasn't heavy.... It didn't make my skin feel extra oily or anything like that. And it also didn't leave my face like after a while, feeling like dry and un-moist” (VC group).

“Oh, that it was just easy. All it was, was just putting it on your face. You don’t have to do much” (trifarotene group).

“So using it at night or using it that one time before I go to bed… I just felt like it cleansed my face…made my face smoother. I also feel like it helped…a lot with my dark spots. I also felt like it was like easier on my face because a lot of products that I've tried in the past, they're harsh… So felt like it made my face smooth” (trifarotene group).

Treatment characteristics least liked by participants included side effects or a worsening of acne during the trial (n = 8/30, 26.7%) (reported by six participants in the trifarotene group [50.0%] and two in the VC group [11.1%]). Three VC group participants did not like the smell of the medication (16.7%). Two participants in the trifarotene group (16.7%) and one in the VC group (5.6%) noted that the time to perceive treatment effect was long.

“So the product itself, I put it on my face. And the very first two weeks, super dry skin, kind of irritating feeling, kind of a burn-y feeling. And then maybe two or three weeks later, it was fine. It didn’t irritate my skin at all” (trifarotene group).

“I did feel like it did take some time because I knew that it wasn't going to disappear overnight. But it did take some time, like a few months” (trifarotene group).

“I didn’t like about it is just the smell of it. It smells like alcohol” (VC group).

Treatment Expectations and Satisfaction

On average, trifarotene group participants (mean [SD] = 8.6 [2.1]) reported higher treatment satisfaction than those in the VC group (7.6 [3.1]), indicating slightly higher satisfaction (1-point difference) with trifarotene treatment (Fig. 2). More participants in the trifarotene group reported being “very satisfied” (n = 7/12, 58.3%) compared to the VC group (n = 6/18, 33.3%). One VC group participant (5.6%) reported being “not satisfied” with the treatment.

“I think an eight because it really helped me, made me feel better, boost my confidence. But then the other I guess two points to it not being a ten is because my skin still isn't as clear as I would like it to be” (VC group).

“I would say 10. It’s definitely improved my skin and my life” (trifarotene group).

Fig. 2.

Overall satisfaction by treatment group. Participants rated their satisfaction with the treatment on a scale of 0–10 (0 = “not satisfied at all” and 10 = “extremely satisfied”). SD standard deviation

All participants in the trifarotene group (n = 12/12, 100.0%) and most in the VC group reported that their expectations were met (n = 16/18, 88.9%). Two VC group participants (11.1%) reported that their expectations were not met because their “hyperpigmentation didn’t get any better” or they thought “it would help more.”

“Because I had expectations about reducing the hyperpigmentation on my skin and it did that” (VC group).

“Because it's helped me get rid of my dark spots, which nothing could help me get rid of my dark spots. So it was a game changer in my life for me, honestly” (trifarotene group).

“I just thought it would help more” (VC group).

All trifarotene group participants who were asked (n = 11/11, 100%) and most in the VC group (n = 15/18, 83.3%) stated that they would recommend the study treatment to others with AIH. Two VC group participants (11.1%) stated that they would not recommend the study treatment as “it didn’t work for me.”

Discussion

The phase 4 LEAP trial of trifarotene (50 μg/g) versus its VC investigated the safety and efficacy of trifarotene in patients with moderate acne and moderate-to-marked AIH [18]. While the primary endpoint for the LEAP trial (reduction in AIH after treatment with trifarotene 50 μg/g) did not achieve statistical significance at week 24 (p = 0.8879), patients treated with trifarotene showed faster improvement in AIH compared with patients treated with VC at week 12. Qualitative data from the current study provide insights into the impact of AIH on patients’ lives, what they considered as meaningful improvement in AIH, and the effect of meaningful treatment on patients’ QoL.

Acne may resolve with sequalae of AIH, erythema, or atrophic scars [3]. AIH occurs at the site of acne inflammatory lesions, and its severity correlates with the severity of the inflammation [25]. Most participants in this study were able to distinguish between the symptoms of acne and AIH (pigment change), and post-inflammatory erythema (residual erythema). AIH can persist for months or years, causing considerable disfigurement and distress to patients, and many patients resort to extreme measures to resolve it [4, 25, 26]. Before the start of trial, over half of the participants rated AIH severity and disturbance in their daily life as ≥ 6.5, suggesting a considerable disease burden. Lower severity and disturbance ratings were observed for Fitzpatrick types II and IV. Participants reported the impact of AIH on all QoL domains, especially the emotional functioning, personal care/hygiene, and social activities or relationships domains. During the trial, most participants perceived a decrease in AIH severity and improvement in all QoL domains. A slightly higher proportion of trifarotene group participants reported a decrease in AIH severity and reduction of AIH disturbance compared to those in the VC group. Participants in both treatment groups described a meaningful improvement in AIH as discoloration fading or becoming lighter/brighter, decrease in the size or number of hyperpigmented areas, and improvement in skin texture (“smooth” skin). A meaningful treatment effect was reflected in a sense of emotional well-being (increased self-confidence and self-esteem) and improvement in social life/relationships.

Participants’ satisfaction with treatment was high in both treatment groups (93%). Most (93%) reported that their treatment expectations were met due to observed efficacy in clearing up skin, improving AIH, reducing irritation and dryness in the skin, and alleviating AIH-related impacts such as low self-confidence and that they would recommend the study treatment to others with AIH. Patients’ preferred treatment attributes included texture (70%), ease of use (60%), treatment effectiveness (53%), and time of effect (37%). Side effects due to treatment or exacerbation of acne were the treatment characteristic least liked by participants (27%).

Participants were patients with moderate acne enrolled in a clinical trial, and their perspectives may differ from patients outside the trial. The sample in this study was small and may not be representative of the population that experiences severe acne and the resulting hyperpigmentation. As all participants in this study were US-based, perspectives of non-US patients regarding their treatment experiences and expectations could not be captured in this study. Although the interviewers did their best to clarify to the trial participants that the interview was regarding their experience with hyperpigmentation rather than symptoms of acne, it is possible that some trial participants may not have been able to distinguish between the two, which could have led to a potential blending of their perception of changes in their skin post-trial and their satisfaction with the study treatment. Participants were interviewed after the completion of the week 24 visit and were asked to share their treatment experience with AIH and its impacts on daily life before and during the trial; therefore, data reported here may have been affected by recall bias (e.g., participants may have omitted some AIH symptoms or impacts, or overestimated the change in AIH after treatment). Nonetheless, the study was conducted by trained interviewers using carefully designed questions intended to help participants recall specific events or experiences with AIH before the trial. For example, participants were reminded of the date of trial enrollment and prompted with anchoring questions to facilitate accurate and relevant responses. Structured prompts were used in this study to improve the precision of the participants’ responses and mitigate recall bias. Anchoring techniques—such as referencing specific dates or events—are well-established in cognitive psychology as effective tools for improving memory accuracy. This methodological approach improves the reliability of data collected in studies that rely on retrospective self-reporting.

Conclusion

This qualitative study provides important insights into the impact of AIH on patients’ lives and how a meaningful treatment effect on AIH translated in a positive effect on how individuals with acne feel and function. Findings suggest that a patient-perceived meaningful improvement in AIH includes aspects such as decrease in skin discoloration as well as the size or area of hyperpigmentation.

All trifarotene-treated patients reported improvements in AIH and that their treatment expectations were met. Trifarotene-treated patients reported high treatment satisfaction, supporting the benefit of trifarotene plus a skincare regimen for the treatment of AIH. However, it should be noted that the VC combined with a skincare regimen also appeared to improve patients’ perceptions of their AIH.

Supplementary Information

Below is the link to the electronic supplementary material.

Funding

This study was funded by Galderma.

Declarations

Conflict of interest

KC, JPY, JP, and RC are employees of Galderma. CDB and NT are employees of Evidera, which was funded by Galderma to conduct this study.

Data sharing statement

The data supporting the findings of this study are available from Evidera. Access to the data may be subject to certain restrictions due to privacy concerns with the sponsor; please contact the corresponding author for further information.

Author contributions

CDB, JPY, RC, and JP contributed to the conception of the study, and CDB, NT, RC, and JP helped develop the methodology. NT managed software. CDB and NT were in charge of the formal analysis, investigation, and data curation. CDB supervised the project, which was administered by NT and KC. KC and RC were responsible for acquiring funding. CDB, NT, KC, JPY, JP, and RC reviewed and edited the manuscript.