Key Summary Points
There is a need for therapies that are efficacious in treating acne but also in preventing and improving acne sequelae. Retinoids are considered by all current guidelines as the cornerstone of acne treatment. |
In phase 3 and 4 clinical studies, trifarotene, a fourth-generation retinoid with retinoic acid receptor (RAR)-γ selectivity, was found to be well tolerated and effective in treating moderate facial and truncal acne, preventing and reducing acne-induced scars (AIS) in patients with moderate-to-severe acne and leading to nominal improvement of acne-induced hyperpigmentation (AIH) at week 12 in patients with moderate acne. |
In the experience-based opinion of the Italian Acne Board, topical trifarotene, used as monotherapy or in combination with other treatments, plays an important role as antiacne therapy in many clinical settings, proving most useful in patients with, or predisposed to, acne sequelae, for its capacity to reduce existing AIS and to impact AIH. Trifarotene is also an option as a long-term treatment for maintenance of remission. |
Introduction
Acne is a highly prevalent, chronic, inflammatory skin disease characterized by a variable clinical presentation and severity. The impact of acne and acne sequelae on patients’ quality of life (QOL) and its important effects on social functioning, interpersonal relationships and mental health have long been recognized [1, 2, 3–4]. Acne-induced scars (AIS) and acne-induced macular hyperpigmentation (AIH, formerly also termed post-inflammatory hyperpigmentation) are a major concern for patients with acne, as they tend to persist beyond remission of active lesions, and scars may be permanent [1]. AIS are mostly atrophic and involve a high proportion of patients, with an estimated prevalence ranging from 43% to 90.8% [1, 5]. Although scarring appears to be significantly correlated with acne severity, it also commonly develops in patients with mild or moderate disease [5]. Other risk factors for AIS include time from acne onset to first effective treatment, relapsing acne, male gender, positive family history for acne, lesion manipulation, trunk localisation and ethnicity [1, 5]. AIH affects more commonly patients with darker Fitzpatrick skin phototypes (FSTs) (IV–VI), with a reported prevalence of 45.5–87.2%, than those with low FSTs, is worsened by sun exposure and is long-lasting (> 1 year in more than half of the patients and > 5 years in nearly a fifth) [1, 6, 7–8]. Although literature data on the burden of AIH are poor, patients often express more concerns about AIH than they do about active acne lesions [6, 9]. Therapies for acne sequelae frequently involve multiple medical or surgical interventions and often lead to poor clinical results. Since prolonged uncontrolled acne is a key risk factor for the development of sequelae, early intervention with an effective treatment is a crucial step to minimizing the risk of scarring and AIH [10, 11].
Topical retinoids are considered as the cornerstone of acne therapy, owing to their multiple effects on the pathophysiology of acne, as also suggested by the recently issued American Academy of Dermatology 2024 guidelines [10, 12]. Recent studies and ongoing research show evidence that retinoids can be effective in the reduction of incidence and severity of AIS and improvement of AIH [9, 13, 14–15]. Trifarotene, a fourth-generation retinoid with selectivity for retinoic acid receptor (RAR)-γ, has proven efficacy in the treatment of facial and truncal acne, with a favourable long-term tolerability profile, and can play an important role in reducing AIS and AIH [14, 15–16].
Though high-quality evidence on the role of topical retinoids in the treatment of acne is available, there is a need for practical suggestions on the use of trifarotene in a patient-centred treatment approach in the Italian real-life setting. To fill this gap, eight experienced dermatologists, members of the Italian Acne Board, convened to review the role of topical retinoids and trifarotene in the treatment of acne and acne sequelae, and to identify and discuss the clinical conditions in which trifarotene could prove most beneficial in real-life practice, based on literature data and their own experience. Suggestions for optimising treatment with trifarotene are also provided.
Commentary
Retinoids: Treatment of Acne and Acne Sequelae
Retinoids are the mainstay of topical acne therapy because of their comedolytic effects, their capacity to resolve the precursor microcomedone lesions and their anti-inflammatory properties, which are exhibited mostly through blockade of several inflammatory pathways, including Toll-like receptor activation, leukocyte migration and AP-1 signalling [17, 18]. The central role of topical retinoids is underscored by their positioning in current guidelines, which recommend the use of these drugs in most clinical settings [10, 12, 19]. Clinical data indicate that topical retinoids may also have activity on acne sequelae, through mechanisms that, though currently not entirely understood, ongoing research is trying to elucidate [9, 13, 14–15, 20]. Inflammation is a recognised crucial factor in the pathogenesis of acne sequelae, and a strong relationship was found between duration of the inflammatory response and severity of scarring [21]. The loss of dermal matrix, which characterizes acne-induced atrophic scars, is believed to occur as an imbalance between synthesis and degradation of extracellular matrix, with a key role being played by matrix metalloproteinases (MMPs) induced by ongoing inflammation [18, 21]. Retinoids modulate immune responses and affect dermal remodelling by stimulating the production of procollagen [13, 18]. Recent studies based on gene expression profiling show that the mechanism by which topical retinoids might reduce scarring includes the downregulation of genes involved in inflammatory chemokines and MMPs, as well as other markers of inflammation which are believed to be implicated in scar formation [22]. In hyperpigmentation disorders, topical retinoids are believed to inhibit the expression of tyrosinase/tyrosinase-related protein 1, thus interrupting melanin synthesis, as well as melanosome transfer to keratinocytes [9, 18, 23].
Before the introduction of trifarotene, few studies have specifically investigated the efficacy of retinoids in reducing AIS or AIH, and best-evidence data are poor. Adapalene 0.3%/benzoyl peroxide (BPO) 2.5% gel for 6 months reduced the number of atrophic scars by approximately 30% compared with vehicle in a randomised, vehicle-controlled, split-face study in 67 patients, with an additional improvement in scar counts after 48 weeks of treatment [13, 24]. In a randomised, active-controlled, split-face study in 36 patients with grade 2–4 atrophic post-acne scars, 6 months’ treatment with 0.1% tazarotene gel or microneedle therapy induced comparable and significant improvements in Goodman and Baron quantitative scores for acne scar severity [25]. The main studies of topical retinoids in patients with post-inflammatory hyperpigmentation (including AIH) were reviewed by Callender et al. [9]. Tazarotene 0.1% cream was found to be more effective than vehicle or 0.3% adapalene in reducing AIH in two randomised, controlled studies [26, 27]. According to a recent consensus document, patients with acne and AIH should receive early treatment with a topical retinoid + BPO [23].
Trifarotene: Pharmacology
Retinoids exert their effects by binding to specific retinoic acid receptors (RARs) and retinoic X receptors (RXRs). Trifarotene is a selective agonist of RAR-γ, with minimal effects on RAR-α and RAR-β, and no effects on RXRs [28]. While the other receptor subtypes are widely expressed in various organs and tissues, RAR-γ is more specific to the skin, where it is mainly expressed in keratinocytes and fibroblasts [23, 29]. Trifarotene selectivity for RAR-γ is more than 20-fold higher than that for RAR-α and RAR-β. In rodent models, trifarotene 0.005% displayed strong comedolytic activity at a concentration tenfold lower than that required for tretinoin to achieve a nearly similar effect. Anti-inflammatory, depigmenting and antipigmenting properties were also demonstrated by trifarotene in vivo in rodent models. Trifarotene was found to be active and stable in human keratinocytes and rapidly metabolised in human liver microsomes, with low systemic concentrations and absence of accumulation over time even when used on large areas of the skin [16, 28]. Notably, in a transcriptomics analysis of biopsies taken from patients with moderate acne of the back who were treated with trifarotene 50 μg/g cream or vehicle, Dréno et al. found that 67 genes (mainly involved in cellular migration, inflammation and matrix remodelling) were specifically regulated (downregulated in nearly all cases) by trifarotene treatment [20, 22]. This is the first clinical study comparing gene expression in normal skin, spontaneously resolving acne lesions and topical retinoid-treated acne lesions. Although trifarotene-treated and spontaneously resolving lesions showed similar changes in cellular expression, trifarotene downregulated genes that were independent of those implicated in spontaneously resolving lesions. Also, only trifarotene treatment modulated SPP1+ macrophages, a subset of macrophages that have been implicated in processes driving fibrosis [20, 22].
Trifarotene: Clinical Studies
The antiacne efficacy and good tolerability of trifarotene were demonstrated in an extensive clinical development programme, including two multicentre, randomised, double-blind, vehicle-controlled, phase 3 trials, PERFECT 1 and PERFECT 2 [30] and a long-term, 52-week safety study, SATISFY [31], in patients with moderate facial and truncal acne. At 12 weeks, the success rates for facial acne were significantly higher in trifarotene vs vehicle recipients (29.4% vs 19.5% in PERFECT 1 and 42.3% vs 25.7% in PERFECT 2; p < 0.001), as were the success rates for truncal acne (35.7% vs 25.0% and 42.6% vs 29.9%, respectively; p < 0.001) [30]. A randomised, double-blind, 12-week, phase 4 study, DUAL [32], evaluated the combination of topical trifarotene with orally administered doxycycline 120 mg/day in patients with severe facial acne, demonstrating a mean absolute change in total lesion counts of − 69.1 in trifarotene + doxycycline recipients vs − 48.1 in patients treated with vehicle + placebo (p < 0.0001) (Table 1).
Table 1. Main studies investigating the efficacy/tolerability of trifarotene in acne and acne sequelae
Study name (location; period) | Design | Participants [age, % female] | Intervention | Main findings |
---|---|---|---|---|
PERFECT 1 [30] (USA, Canada, Europe, Russia; 2015–2017) | Multicentre, randomised, double-blind, vehicle-controlled study | 1208 pts with moderate facial and truncal acne [≥ 9 years, mean 19.4–52.1%] | Trifarotene 50 μg/g cream OD vs vehicle OD for 12 weeks | Primary endpoints: IGA success rates (face) were 29.4% in trifarotene group vs 19.5% in vehicle group, mean absolute change in facial inflammatory lesion count was − 19.0 (− 54.4%) vs − 15.4 (− 44.8%), mean absolute change in facial non-inflammatory lesion count was − 25.0 (− 49.7%) vs − 17.9 (− 35.7%) (p < 0.001 for all) Secondary endpoints: PGA success rates (trunk) were 35.7% in trifarotene group vs 25.0% in vehicle group, mean absolute change in truncal inflammatory lesion count was − 21.4 (− 57.4%) vs − 18.8 (− 50.0%), mean absolute change in facial non-inflammatory lesion count was − 21.9 (− 49.1%) vs − 17.8 (− 40.3%) (p < 0.001 for all) |
PERFECT 2 [30] (USA, Canada, Europe, Russia; 2015–2017) | Multicentre, randomised, double-blind, vehicle-controlled study | 1212 pts with moderate facial and truncal acne [≥ 9 years, mean 19.7–57.3%] | Trifarotene 50 μg/g cream OD vs vehicle OD for 12 weeks | Primary endpoints: IGA success rates (face) were 42.3% in trifarotene group vs 25.7% in vehicle group, mean absolute change in facial inflammatory lesion count was − 24.2 (− 66.2%) vs − 18.7 (− 51.2%), mean absolute change in facial non-inflammatory lesion count was − 30.1 (− 57.7%) vs − 21.6 (− 43.9%) (p < 0.001 for all) Secondary endpoints: PGA success rates (trunk) were 42.6% in trifarotene group vs 29.9% in vehicle group, mean absolute change in truncal inflammatory lesion count was − 25.5 (− 65.4%) vs − 19.8 (− 51.1%), mean absolute change in facial non-inflammatory lesion count was − 25.9 (− 55.2%) vs − 20.8 (− 45.1%) (p < 0.001 for all) |
SATISFY [31] (Europe, USA; 2015–2017) | Multicentre, prospective, open-label study | 453 pts with moderate facial and truncal acne [≥ 9 years, mean 18.3–49.9%] | Trifarotene 50 μg/g cream OD for 52 weeks | Both IGA and PGA success rates continuously improved over time: IGA from 26.6% at week 12 to 65.1% at week 52, PGA from 38.6% at week 12 to 66.9% at week 52. Overall success (IGA + PGA in the same pt) was 57.9% at week 52 76.5% of pts completed the study. Cutaneous TEAEs (none serious) were reported in 12.6% of pts. Scores for local irritation peaked during first week of treatment on the face, and up to weeks 2–4 on the trunk. At the last visit, 53.8–54.2% of pts had scores of 0–1 (i.e. no effect of acne on QOL) according to DLQI or C-DLQI |
DUAL [32] (USA; 2020–2021) | Multicentre, randomised (2:1 ratio), double-blind, controlled study | 202 pts with severe facial acne [≥ 12 years, mean 20.0/20.3- 60.2%−62.3%] | Trifarotene 50 μg/g cream + doxycycline 120 mg/day PO OD vs vehicle + placebo OD for 12 weeks | Primary endpoint: Mean absolute change from baseline in total facial lesion count was − 69.1 (− 67.0%) for the trifarotene + doxycycline (T + D) group vs − 48.1 (− 45.5%) in the vehicle + placebo (V + P) group (p < 0.0001) Secondary endpoints: Mean absolute change in facial inflammatory lesion count was − 29.4 in the T + D group vs − 19.5 in the V + P group, mean absolute change in facial non-inflammatory lesion count was − 39.5 vs − 28.2 (p < 0.0001 for all). IGA success rates were 31.7% in the T + D group vs 15.8% in the V + P group (p < 0.05) The tolerability profile was comparable between treatment arms |
START [14] (USA, Canada, France; 2021–2023) | Multicentre, randomised, double-blind, vehicle-controlled, split-face study | 121 pts with moderate-to-severe facial acne [17–34 years, mean 22.9–72.7%] | Trifarotene 50 μg/g cream OD vs vehicle OD for 24 weeks | Primary endpoint: Mean absolute change from baseline to week 24 in total atrophic scar count per half face was − 5.9 (− 55.2%) for trifarotene-treated (T) sides vs − 2.7 (− 29.9%) for vehicle-treated (V) sides (p < 0.0001) Secondary endpoints: SGA success rates were 31.3% for T sides vs 8.1% for V sides (p < 0.001). IGA success rates were 63.6% for T sides vs 31.3% for V sides, mean change in total acne lesion count was − 70.0% vs − 44.9%, mean change in inflammatory lesion count was − 76.3% vs − 48.3%, mean change in non-inflammatory lesion count was − 61.4% vs − 32.1% (p < 0.05 for all) |
LEAP [15] (Spain, USA; 2021–2022) | Multicentre, randomised, double-blind, vehicle-controlled study | 123 pts with moderate facial acne [13–35 years, mean 22.7/21.9–75.0%/76.2%] | Trifarotene 50 μg/g cream OD vs vehicle OD for 24 weeks | Primary endpoint: Mean absolute change from baseline to week 24 in AIH ODS scores was not significantly different between treatment arms Secondary endpoints: Percent change from baseline to week 24 in total PAHPI scores was − 18.9% for trifarotene-treated pts vs − 11.3% for vehicle-treated pts (p < 0.01). IGA success rates at week 24 were 61.1% in the trifarotene group vs 39.4% in the vehicle group (p < 0.05) |
IGA, PGA or SGA success = clear/almost clear and ≥ 2-grade improvement
AIH ODS Overall Disease Severity Hyperpigmentation Scale, DLQI Dermatology Life Quality Index, C-DLQI Children DLQI, IGA Investigator Global Assessment, PAHPI Postacne Hyperpigmentation Index, PGA Physician Global Assessment, SGA Scar Global Assessment, TEAEs treatment-emergent adverse events
Trifarotene: Clinical Studies in AIS
There is a dearth of high-quality evidence for effective interventions in the prevention and management of acne sequelae [1]. Several therapeutical approaches have been described for improvement of acne scars, including chemical exfoliation, microneedling, lasers, dermal fillers and other surgical or medical procedures, but a complete correction is rarely achieved [10, 21, 33, 34]. Furthermore, some energy-based devices can induce, or worsen, hyperpigmentation [33].
A recent phase 4 clinical study supports the use of trifarotene in patients with AIS [14]. The START study, a multicentre, randomised, split-face, double-blind clinical trial in patients with moderate-to-severe acne (Investigator Global Assessment [IGA] score = 3 or 4) and existing atrophic scars ≥ 2 mm2 (≥ 10 in total) evaluated the efficacy and tolerability of 6 months’ treatment with trifarotene in reducing scars [14] (Table 1). Acne scar severity according to Scar Global Assessment (SGA) was mostly mild or moderate. Patients (n = 121) were instructed to apply trifarotene 50 μg/g cream to one randomised side of the face and vehicle to the other one. Applications were videotaped by patients to ensure treatment compliance. Skincare products, consisting of a gentle cleanser, an oil-absorbing moisturiser with SPF30 and a moisturising lotion (Cetaphil®), were also provided to patients, while allowing them to use a different skincare routine if desired. All the study outcomes resulted in favour of trifarotene. At week 24, the mean absolute change from baseline in atrophic scar count (primary endpoint) was − 5.9 for the trifarotene-treated side compared with − 2.7 for the vehicle-treated side, with a difference between treatment arms of 3.2 (p < 0.0001). The difference between treatment arms was statistically significant as early as week 2 and increased throughout the study. Secondary endpoints also favoured the active treatment. The total scar count by week 24 was 5.4 for trifarotene-treated sides vs 9.1 for the control sides (corresponding to reductions from baseline by 55.2% vs 29.9%, respectively). At the end of the study, SGA success rates (defined as a SGA score of clear/almost clear and ≥ 2 grade improvement) were 31.3% vs 8.1% (p < 0.001). Although the study was not powered for the assessment of treatment-related effects on acne lesions, trifarotene was significantly more effective than vehicle in reducing total lesion counts (starting from week 1), inflammatory lesion counts (from week 2) and non-inflammatory lesion counts (from week 1), while IGA success rates by the end of the study were 63.6% vs 31.3%, respectively (p < 0.05). As for patient-reported outcomes, the mean severity rating for scars was 4.9 at baseline for both arms, and decreased to 1.9 for trifarotene vs 2.6 for vehicle at the end of the study. Trifarotene was well tolerated, with treatment-emergent adverse events (none severe) occurring in 5.8% of the active treatment sides vs 2.5% in the control sides. Mean scores for erythema, scaling, dryness and burning/stinging, which were mostly mild or moderate, peaked at week 2, decreasing thereafter [14].
Trifarotene: Clinical Studies in AIH
Therapy of AIH should be started early. Various topical agents as well as chemical peelings, microdermabrasion, microneedling and energy-based devices have demonstrated some benefit in the treatment of AIH [10, 23, 35]. According to some Italian Acne Board members’ experience, a 6–12 months’ treatment with azelaic acid 15% aqueous gel is an effective and safe approach to treatment of AIH. Apart from retinoids, recommended treatments for AIH have no or limited activity in the treatment of acne.
A recent phase 4 multicentre, randomised, vehicle-controlled, double-blind clinical trial (LEAP) in patients with moderate acne (IGA score = 3) and acne-induced AIH evaluated the efficacy and tolerability of trifarotene in improving AIH [15]. In the study, 123 subjects with an Overall Disease Severity Hyperpigmentation Scale (AIH ODS) score of 4–6 were randomised to treatment with trifarotene 50 μg/g cream or vehicle for 24 weeks (Table 1). They were instructed to apply trifarotene or vehicle once daily at night time, together with a skincare regimen consisting of a gentle cleanser, a moisturising lotion and sunscreen products with SPF30 (Cetaphil®). Patients had on average approximately 27–30 AIH lesions, with an average size of approximately 2 mm2. All FSTs were represented, although participating investigators were asked to enrol ≥ 70% of subjects with dark skin phototypes. At the end of the study, AIH ODS scores improved in both groups but there was no statistically significant difference between treatment arms regarding the absolute change from baseline in AIH ODS score, the primary study endpoint. A significant difference between groups in AIH ODS score mean percent change was observed at week 12 (− 34.4% vs − 23.6%; p = 0.03) but not at week 24 (− 45.4% vs − 44.9%). There was, however, a significant improvement in favour of trifarotene vs vehicle on a secondary endpoint, the Post-Acne Hyperpigmentation Index (PAHPI), a detailed hyperpigmentation assessment parameter which evaluates size, intensity and number of the AIH lesions [36]. Mean percent change from baseline to week 24 in total PAHPI score was − 18.9% in trifarotene-treated patients vs − 11.3% in vehicle recipients (p = 0.0093). Trifarotene was also effective in reducing acne lesions, with significantly higher IGA success rates in the trifarotene arm vs vehicle. Both investigators and patients observed an improvement in AIH lesions at the end of the study, with scores of ‘slightly lighter’ to ‘much lighter’ on the AIH improvement scale reported by > 90% in the trifarotene group and > 80% in the vehicle group. Trifarotene demonstrated an excellent tolerability profile (probably also due to the protocol-required use of skincare products by all the study patients) with mean scores for erythema, scaling, dryness and burning/stinging remaining < 0.5 even during the first weeks of treatment. In exit interviews about perceived changes in AIH since starting treatment, appreciation was frequently expressed for the improvement in skin quality (i.e. more uniform skin, lighter and more even skin tone, fewer imperfections) [15]. It should be noted that the adoption of an appropriate holistic skincare regimen based on cleansing, treatment, moisturisation and photoprotection (CTMP) contributed to the positive outcomes observed in this study [37].
Trifarotene in Personalised Acne Therapy
Prevention and reduction of acne sequelae represents a key aspect in acne management. Risk factors that are particularly relevant for the development and severity of acne sequelae include family history of scars, long-standing inflammation, darker skin phototype and sun exposure. Tanning is popular among Italians, who frequently underestimate the risks associated with solar ultraviolet radiation and often fail to adopt sun protection practices [38, 39]. Misconceptions about acne held by patients often delay consultation with a dermatologist and early implementation of an effective therapy, thus promoting the development of AIS and AIH. In an Italian survey investigating knowledge and beliefs about acne and its treatment in both 2327 patients with acne and their mothers, only 8% of the mothers considered a dermatologist-prescribed therapy as the best treatment for their child, and a physician’s consultation was deemed necessary by the mothers only when acne was severe (43%) or previous treatments had failed (26%) [40].
In the authors’ experience, AIH is not as frequently observed in Italian patients as it is in populations with a high prevalence of darker skin phototypes. AIS, on the contrary, represent a common problem that needs to be discussed with patients and their parents or carers, who are concerned about the possibility of permanent scars. Patients (and parents), especially those with a family history of scars, are often already aware of this risk.
Since its approval in Italy in 2020, trifarotene has proven to be a valuable additional option in personalised acne therapy. Based on pharmacological characteristics, clinical data and the authors’ experience, trifarotene may be considered as an important option in the following facial and truncal acne scenarios in patients predisposed to AIS or AIH or those with existing AIS or AIH lesions:
Mild-to-moderate varieties
Moderate-to-severe varieties
Severe (nodular) varieties
Maintenance treatment
In association with cosmetic procedures for acne sequelae
Below is a more detailed overview of the potential role of trifarotene in specific clinical presentations of acne and associated sequelae.
Clinical Scenarios
Mild-to-Moderate Acne
According to the authors’ experience, trifarotene (as monotherapy) is an option to be considered for the treatment of retentional, comedonal and/or papular facial and truncal acne (including acne occurring in adult women) (Fig. 1). From a practical point of view, the presence of a pump dispenser in the commercially available trifarotene formulation facilitates application of the correct amount of active ingredient—an important aspect in topical retinoid therapy—for the treatment of both the face and large areas of the body (particularly the back).
[See PDF for image]
Fig. 1
Advanced digital photography of a 25-year-old female patient with mild inflammatory acne refractory to previous treatment with benzoyl peroxide 5% gel (right side of the face, target lesions circled): A at baseline; B clear response after 12 weeks of once-daily evening application of trifarotene 0.005% cream
Notably, the evidence provided by the latest clinical studies regarding trifarotene efficacy in preventing and reducing acne sequelae makes this drug our first choice in patients at risk for scarring (based on personal or family history) or AIH (Fig. 2).
[See PDF for image]
Fig. 2
Advanced digital photography of a 22-year-old male patient with acne-induced macular hyperpigmentation (AIH) different topical treatment (forehead, target lesions circled): A at baseline; B no evident signs of AIH after 12 weeks of once-daily evening application of trifarotene 0.005% cream
Moderate-to-Severe Acne
In this clinical variety of acne, an oral antibiotic may be associated with the topical treatment. As previously seen, trifarotene has been used successfully in combination with an oral antibiotic in severe acne [32]. When selecting topical treatments for facial acne, trifarotene could represent an option, especially if scars are already present. However, a fixed combination of topical retinoid + antimicrobial agent (such as 0.3% adapalene/2.5% BPO, or 1.2% clindamycin/0.025% tretinoin) could offer the advantage of a faster onset of action in reducing inflammatory lesions, thus preventing the risk of scarring. In combined facial and truncal acne, treatment selection should take into account acne severity on each site. Dermatologists could opt for prescribing 0.3% adapalene/2.5% BPO for the face and trifarotene for the trunk (switching to trifarotene for both sites once the inflammatory lesions on the face have resolved) or just trifarotene, if the patient would rather use a single product for face and trunk (Fig. 3).
[See PDF for image]
Fig. 3
Advanced digital photography of a 27-year-old male patient with pustular-nodular facial acne (right side of the face and chin, target lesions circled): A at baseline; B clear response of nodules after 12 weeks of once-daily evening application of trifarotene 0.005% cream
Severe (Nodular) Acne
Orally administered isotretinoin is the treatment of choice in this setting and its benefits in terms of clearing acne lesions and achieving long remission periods have been highlighted in all clinical guidelines [10, 12, 19]. Trifarotene should not be considered as equivalent to systemic retinoids but may have a role as a topical treatment for facial and truncal acne or combined facial and truncal acne when selecting a treatment strategy based on a topical therapy (retinoid or fixed-dose combination) + oral antibiotic in patients who have severe non-nodulocystic acne and cannot be treated with orally administered isotretinoin therapy for any reasons [41] (Figs. 4, 5).
[See PDF for image]
Fig. 4
Advanced digital photography of a 30-year-old male patient with papular-pustular acne on the trunk (left scapular area, target lesions circled): A at baseline; B clear response of nodules after 20 weeks of once-daily evening application of trifarotene 0.005% cream
[See PDF for image]
Fig. 5
Advanced digital photography of a 30-year-old male patient with pustular-nodular acne and multiple scars on the trunk (target nodules [a] and scars [b] circled): A at baseline; B clear response of target lesions after 20 weeks of once-daily evening application of trifarotene 0.005% cream
Maintenance Treatment
The long-term tolerability and the continuous, time-dependent efficacy with absence of a plateau effect, as demonstrated in the 52-week SATISFY study [31], make trifarotene a particularly useful candidate in the long-term management of acne. In the authors’ experience, a 9-month treatment with trifarotene proved to be well tolerated and effective in preventing acne recurrence after isotretinoin therapy in a series of approximately 80 patients. The maintenance treatment was initiated approximately 1 month after stopping isotretinoin.
Trifarotene in Association with Cosmetic Procedures in Acne Sequelae
The ability of retinoids to modulate collagen synthesis and degradation, among other skin functions (hence their use in the treatment of photoaged skin), is well known. Trifarotene has been shown to modulate molecular pathways involved in extracellular matrix reorganisation and fibrosis, which may partly explain its activity in minimising scar development and abnormal collagen remodelling processes [20]. These pharmacological properties suggest that trifarotene may demonstrate synergistic effects when used in association with procedures aimed at the correction of long-lasting scars left after the resolution of acne. Promising results were observed in 10 patients with post-acne slightly hyperpigmented atrophic scars who underwent 3 months’ treatment with trifarotene followed by an injectable hyaluronic acid-based skin booster (3–10 sessions in total) [42]. Although more evidence is needed for the inclusion of trifarotene in protocols (with and without energy-based devices) to improve acne scars, this retinoid may have a role as at-home therapy between multiple treatment sessions, or as maintenance treatment after the completion of the corrective procedures.
How to Minimise Trifarotene-Induced Local Irritation
Local skin irritation is very common when first using retinoids and should always be discussed with the patient before initiating treatment [43]. As previously seen, local irritation associated with trifarotene (mostly manifesting as erythema, scaling, dryness and burning/stinging) is generally mild or moderate, peaks at week 1–3 for the face and declines thereafter, when tolerance develops [14, 16, 31]. In acne of the trunk, local irritation is uncommon and mild. The first 2–3 weeks of treatment are therefore crucial for patient compliance, and efforts should be made to minimise the occurrence of local side effects and encourage treatment adherence. Patients should be advised to start treatment every other day, titrating upwards according to tolerability. Several measures can be adopted to minimise skin irritation during the first weeks of trifarotene treatment. Explicative leaflets on the correct use of retinoids and electronic devices (e.g. text messages) are useful tools for minimising adverse reactions and increasing treatment adherence [44]. Some practical suggestions, including short-contact therapy [45], reduced frequency of application, treatment interruption for a few days and use of appropriate skin care, are listed in Table 2.
Table 2. Practical suggestions to minimise retinoid-induced skin irritation
Always inform the patients about side effects of retinoids |
Specify amount of drug to be used on single regions of the face or body |
Provide the patient with written instructions |
Instruct the patient to: |
Apply the treatment overnight, avoiding eye contour, perioral areas and neck |
Apply treatment ≥ 1 h before going to bed, to avoid pillow-transfer of drug to sensitive areas |
Apply treatment every other day for first 2–3 weeks |
Use appropriate skin care products (gentle cleanser, moisturising lotion and moisturiser with SPF ≥ 30 during the day) |
If irritation is a concern, instruct the patient to: |
Use short-contact therapy, washing the face ≤ 30 min after application |
Reduce frequency of application |
In case of severe irritation, interrupt treatment for 3–4 days, resuming it afterwards with reduced frequency |
Dermocosmetics and photoprotection play an important role during treatment with retinoids and promote treatment adherence [46, 47]. Although retinoids are not photosensitising molecules in the photochemical sense, by reducing the thickness of the stratum corneum they allow the transmission of larger quantities of solar radiation (in particular ultraviolet) to the underlying skin layers, thus inducing erythematous reactions. Moreover, it is important to not interrupt antiacne treatment during summertime. Therefore, dermatologists should recommend daytime use of a non-comedogenic moisturiser with SPF ≥ 30 [46]. In the clinical trials of trifarotene, as previously seen, patients were provided with a defined skincare regimen consisting of a gentle cleanser and moisturising lotions with photoprotection (SPF30), with the flexibility to use their preferred skincare regimen, which explains the low irritability scores and high treatment compliance [14, 15–16]. As recently highlighted, an integrated holistic skincare routine based on the CTMP approach (i.e. gentle cleansing, prescription treatment, moisturisation and daily photoprotection) offers several advantages in the management of acne, such as reduction of inflammation, prevention of the appearance of new lesions and strengthening of the skin barrier function, with reduction of treatment-related side effects [37].
Conclusion
Trifarotene, the only retinoid with RAR-γ selectivity available so far, has been evaluated in an extensive clinical programme and proven to be effective and well tolerated in treating facial and truncal acne and in preventing and reducing acne sequelae when used in patients with active acne. The perceived benefits of trifarotene treatment and its favourable tolerability profile were also apparent in patient-reported outcomes. The authors’ clinical experience in dermatological practices in Italy confirms that this fourth-generation retinoid is an important addition to the armamentarium of antiacne topical therapies that can be used alone or in association with other treatments in multiple clinical settings, proving most valuable in patients with existing scars or predisposed to scarring and AIH, and as a long-term treatment for maintaining remission.
Acknowledgements
The authors thank the patients who gave consent to the use of their images
Medical Writing and Editorial Assistance
Medical writing and editorial assistance for this manuscript was provided by Dr. Elena Scotti of Editamed srl and funded by Galderma Italia S.p.A.
Author Contributions
All authors; Maria Carmela Annunziata, Mauro Barbareschi, Vincenzo Bettoli, Federica Dall’Oglio, Giuseppe Micali, Giuseppe Monfrecola, Nevena Skroza Matteo Tretti Clementoni & Stefano Veraldi contributed to the study design and participated in all stages of manuscript preparation.
Funding
This commentary and the journal’s Rapid Service Fee were funded by Galderma Italia S.p.A.
Data Availability
There are no additional data associated with this study beyond those presented in this article.
Declarations
Conflict of Interest
Dr. Barbareschi, Dr. Micali and Dr. Monfrecola have no competing interests to declare. Dr. Annunziata has acted as a consultant for Bionike, Pierre Fabre and La Roche Posay. Dr. Bettoli has acted as a consultant, advisory board member and/or investigator for Exeltis, Menarini, AbbVie, Beiersdorf, Biogena, Difa Cooper, Galderma, Ganassini, Giuliani, L'Oréal, Pierre-Fabre, Novartis and UCB. Dr. Dall’Oglio has acted as a consultant for Eli Lilly, AbbVie, Cantabria Labs, Difa Cooper, La Roche Posay, Pierre Fabre and Bioderma. Dr. Skroza has acted as a consultant, advisory board member and/or investigator for AbbVie, Boehringer-Ingelheim, Galderma, Janssen, Leo Pharma, L'Oréal, Novartis and Sanofi. Dr. Tretti Clementoni has acted as a consultant for Lumenis, Quanta System, ExoCobio, Deka, Galderma, Sinclair, Sofwave, and Lutronic. Dr. Veraldi has acted as a consultant for Bionike, BMG Pharma, Cantabria Labs Difa Cooper, Cieffederma, Damor, Exeltis, Ganassini, GD, Ideka, La Roche Posay, Substipharm, and Tillomed. None of the authors has competing interests to declare regarding this study.
Ethical Approval
Ethics committee approval was not required because this article is based on previously conducted studies. Patients and/or guardians provided written informed consent for the publication of the images.
References
1. Layton, A; Alexis, A; Baldwin, H et al. Identifying gaps and providing recommendations to address shortcomings in the investigation of acne sequelae by the Personalising Acne: Consensus of Experts panel. JAAD Int; 2021; 5, pp. 41-48. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/34816133][PubMedCentral: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593750]
2. Fabbrocini, G; Cacciapuoti, S; Monfrecola, G. A qualitative investigation of the impact of acne on Health-Related Quality of Life (HRQL): development of a conceptual Model. Dermatol Ther (Heidelb); 2018; 8, pp. 85-99. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29435857]
3. Layton, AM; Thiboutot, D; Tan, J. Reviewing the global burden of acne: how could we improve care to reduce the burden?. Br J Dermatol; 2021; 184, pp. 219-225.1:STN:280:DC%2BB38fjtVanuw%3D%3D [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32770673]
4. Tan, J; Beissert, S; Cook-Bolden, F et al. Evaluation of psychological well-being and social impact of atrophic acne scarring: a multinational, mixed-methods study. JAAD Int; 2021; 6, pp. 43-50. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/35005652][PubMedCentral: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8719008]
5. Tan, J; Kang, S; Leyden, J. Prevalence and risk factors of acne scarring among patients consulting dermatologists in the USA. J Drugs Dermatol; 2017; 16, pp. 97-102. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28300850]
6. Abad-Casintahan, F; Chow, SK; Goh, CL et al. Frequency and characteristics of acne-related post-inflammatory hyperpigmentation. J Dermatol; 2016; 43, pp. 826-828. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26813513]
7. Elbuluk, N; Grimes, P; Chien, A et al. The pathogenesis and management of acne-induced post-inflammatory hyperpigmentation. Am J Clin Dermatol; 2021; 22, pp. 829-836. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/34468934]
8. da Rocha, MAD; Fierro-Arias, L; Cohen Sabban, EN; Castillo, RS; Chavda, R; Almeida, LM. Acne characteristics in Latin American patients and the potential role of trifarotene. Int J Dermatol; 2023; 62, pp. 1176-1185. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/37340535]
9. Callender, VD; Baldwin, H; Cook-Bolden, FE; Alexis, AF; Stein Gold, L; Guenin, E. Effects of topical retinoids on acne and post-inflammatory hyperpigmentation in patients with skin of color: a clinical review and implications for practice. Am J Clin Dermatol; 2022; 23, pp. 69-81. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/34751927]
10. Thiboutot, DM; Dréno, B; Abanmi, A et al. Practical management of acne for clinicians: an international consensus from the Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol; 2018; 78,
11. Tan, J; Alexis, A; Baldwin, H et al. The personalised acne care pathway-recommendations to guide longitudinal management from the personalising acne: consensus of experts. JAAD Int; 2021; 5, pp. 101-111. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/34816135][PubMedCentral: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593752]
12. Reynolds, RV; Yeung, H; Cheng, CE et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol; 2024; S0190–9622,
13. Dréno, B; Bissonnette, R; Gagné-Henley, A et al. Prevention and reduction of atrophic acne scars with adapalene 0.3%/benzoyl peroxide 2.5% gel in subjects with moderate or severe facial acne: results of a 6-month randomized, vehicle-controlled trial using intra-individual comparison. Am J Clin Dermatol; 2018; 19, pp. 275-286. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29549588][PubMedCentral: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5978908]
14. Schleicher, S; Moore, A; Rafal, E et al. Trifarotene reduces risk for atrophic acne scars: results from a phase 4 controlled study. Dermatol Ther (Heidelb); 2023; 13, pp. 3085-3096. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/37838987]
15. Alexis A, Del Rosso JQ, Forman S, et al. Importance of treating acne sequelae in skin of color: 6-month phase IV study of trifarotene with an appropriate skincare routine including UV protection in acne-induced post-inflammatory hyperpigmentation. Int J Dermatol. 2024;63(6):806–15.
16. Tan, J; Chavda, R; Baldwin, H; Dreno, B. Management of acne vulgaris with trifarotene. J Cutan Med Surg; 2023; 27, pp. 368-374. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/36927117][PubMedCentral: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486177]
17. Zaenglein, AL; Pathy, AL; Schlosser, BJ et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol; 2016; 74, pp. 945-973. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26897386]
18. Leyden, J; Stein-Gold, L; Weiss, J. Why topical retinoids are mainstay of therapy for acne. Dermatol Ther (Heidelb); 2017; 7, pp. 293-304. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28585191]
19. Nast, A; Dréno, B; Bettoli, V et al. European evidence-based (S3) guideline for the treatment of acne-update 2016-short version. J Eur Acad Dermatol Venereol; 2016; 30, pp. 1261-1268.1:STN:280:DC%2BC2s3pvFyrtQ%3D%3D [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27514932]
20. Dreno, B; Chavda, R; Julia, V; Khammari, A; Blanchet-Réthoré, S; Krishnaswamy, JK. Transcriptomics analysis indicates trifarotene reverses acne-related gene expression changes. Front Med (Lausanne); 2021; 8, [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/34746181]745822.
21. Fabbrocini, G; Cacciapuoti, S. Evaluation, prevention, and management of acne scars: issues, strategies, and enhanced outcomes. J Drugs Dermatol; 2018; 17,
22. Dréno, B; Zouboulis, CC; Tan, J; Baldwin, H; Krishnaswamy, JK; Chavda, R. Role of retinoic acid receptor subtypes in the pathophysiology of acne. J Drugs Dermatol; 2023; 22, pp. 608-614. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/37276160]
23. Taylor, S; Elbuluk, N; Grimes, P et al. Treatment recommendations for acne-associated hyperpigmentation: results of the Delphi consensus process and a literature review. J Am Acad Dermatol; 2023; 89, pp. 316-323. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/36924935]
24. Dréno, B; Bissonnette, R; Gagné-Henley, A et al. Long-term effectiveness and safety of up to 48 weeks' treatment with topical adapalene 03.%/benzoyl peroxide 2.5% gel in the prevention and reduction of atrophic acne scars in moderate and severe facial acne. Am J Clin Dermatol; 2019; 20, pp. 725-732. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31209851]
25. Afra, TP; Razmi, TM; Narang, T; Dogra, S; Kumar, A. Topical tazarotene gel, 0.1%, as a novel treatment approach for atrophic postacne scars: a randomized active-controlled clinical trial. JAMA Facial Plast Surg; 2019; 21, pp. 125-132.1:STN:280:DC%2BB3crisVWmtg%3D%3D [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30452511]
26. Grimes, P; Callender, V. Tazarotene cream for postinflammatory hyperpigmentation and acne vulgaris in darker skin: a double-blind, randomized, vehicle-controlled study. Cutis; 2006; 77, pp. 45-50. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16475496]
27. Tanghetti, E; Dhawan, S; Green, L et al. Randomized comparison of the safety and efficacy of tazarotene 0.1% cream and adapalene 0.3% gel in the treatment of patients with at least moderate facial acne vulgaris. J Drugs Dermatol; 2010; 9, pp. 549-558. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20480800]
28. Aubert, J; Piwnica, D; Bertino, B et al. Nonclinical and human pharmacology of the potent and selective topical retinoic acid receptor-γ agonist trifarotene. Br J Dermatol; 2018; 179, pp. 442-456.1:CAS:528:DC%2BC1cXhsFOgs7zM [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29974453]
29. Cosio, T; Di Prete, M; Gaziano, R et al. Trifarotene: a current review and perspectives in dermatology. Biomedicines; 2021; 9, 237.1:CAS:528:DC%2BB3MXhtlyhurfM [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/33652835][PubMedCentral: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996910]
30. Tan, J; Thiboutot, D; Popp, G et al. Randomized phase 3 evaluation of trifarotene 50 μg/g cream treatment of moderate facial and truncal acne. J Am Acad Dermatol; 2019; 80, pp. 1691-1699.1:CAS:528:DC%2BC1MXhtVWqtbfL [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30802558]
31. Blume-Peytavi, U; Fowler, J; Kemény, L et al. Long-term safety and efficacy of trifarotene 50 μg/g cream, a first-in-class RAR-γ selective topical retinoid, in patients with moderate facial and truncal acne. J Eur Acad Dermatol Venereol; 2020; 34, pp. 166-173.1:CAS:528:DC%2BB3cXhtl2jsrc%3D [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31306527]
32. Del Rosso, JQ; Johnson, SM; Schlesinger, T et al. A randomized, controlled trial of trifarotene plus doxycycline for severe acne vulgaris. J Clin Aesthet Dermatol; 2022; 15, pp. E53-E59. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/35942016][PubMedCentral: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345187]
33. Salameh, F; Shumaker, PR; Goodman, GJ et al. Energy-based devices for the treatment of acne scars: 2022 international consensus recommendations. Lasers Surg Med; 2022; 54, pp. 10-26. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/34719045]
34. Almukhadeb, E; Binkhonain, F; Alkahtani, A; Alhunaif, S; Altukhaim, F; Alekrish, K. Dermal fillers in the treatment of acne scars: a review. Ann Dermatol; 2023; 35, pp. 400-407.1:CAS:528:DC%2BB2cXptlehtLY%3D [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/38086353][PubMedCentral: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10733075]
35. Davis, EC; Callender, VD. A review of acne in ethnic skin: pathogenesis, clinical manifestations, and management strategies. J Clin Aesthet Dermatol; 2010; 3, pp. 24-38. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20725545][PubMedCentral: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921746]
36. Savory, SA; Agim, NG; Mao, R et al. Reliability assessment and validation of the postacne hyperpigmentation index (PAHPI), a new instrument to measure postinflammatory hyperpigmentation from acne vulgaris. J Am Acad Dermatol; 2014; 70, pp. 108-114. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24176524]
37. Goh CL, Wu Y, Welsh B, et al. Challenges and real-world solutions for adoption of holistic skincare routine (cleansing, treatment, moisturization, and photoprotection) in acne, rosacea, atopic dermatitis, and sensitive skin: an expert consensus. J Cosmet Dermatol. 2024;23(8):2516–23.
38. Suppa, M; Cazzaniga, S; Fargnoli, MC; Naldi, L; Peris, K. Knowledge, perceptions and behaviours about skin cancer and sun protection among secondary school students from Central Italy. J Eur Acad Dermatol Venereol; 2013; 27, pp. 571-579.1:STN:280:DC%2BC38vjvV2guw%3D%3D [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22356655]
39. Modenese, A; Loney, T; Ruggieri, FP; Tornese, L; Gobba, F. Sun protection habits and behaviors of a group of outdoor workers and students from the agricultural and construction sectors in north-Italy. Med Lav; 2020; 111, pp. 116-125. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32352425][PubMedCentral: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810007]
40. Tavecchio, S; Barbareschi, M; Veraldi, S. What Italians think about acne: results of a survey on 2327 acne patients and their mothers. G Ital Dermatol Venereol; 2020; 155, pp. 642-645. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30621386]
41. Del Rosso, JQ; Stein Gold, L; Johnson, SM et al. Efficacy and safety of adapalene 0.3%/benzoyl peroxide 2.5% gel plus oral doxycycline in subjects with severe inflammatory acne who are candidates for oral isotretinoin. J Drugs Dermatol; 2018; 17, pp. 264-273. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29537444]
42. Belmontesi, M. Sequential treatment with topical trifarotene and injectable NASHA gel in acne scars: a case series. J Drugs Dermatol; 2023; 22, pp. 502-506. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/37133474]
43. Veraldi, S; Brena, M; Barbareschi, M. Allergic contact dermatitis caused by topical antiacne drugs. Expert Rev Clin Pharmacol; 2015; 8, pp. 377-381.1:CAS:528:DC%2BC2MXhtVCmtbrK [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25982754]
44. Donnarumma, M; Fattore, D; Greco, V et al. How to increase adherence and compliance in acne treatment? A combined strategy of SMS and visual instruction leaflet. Dermatology; 2019; 235, pp. 463-470.1:CAS:528:DC%2BC1MXitFeqsr3O [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31586999]
45. Veraldi, S; Barbareschi, M; Benardon, S; Schianchi, R. Short contact therapy of acne with tretinoin. J Dermatolog Treat; 2013; 24,
46. Del Rosso, JQ; Gold, M; Rueda, MJ; Brandt, S; Winkelman, WJ. Efficacy, safety, and subject satisfaction of a specified skin care regimen to cleanse, medicate, moisturize, and protect the skin of patients under treatment for acne vulgaris. J Clin Aesthet Dermatol; 2015; 8, pp. 22-30. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25610521][PubMedCentral: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295855]
47. Araviiskaia, E; Layton, AM; Estebaranz, JLL; Ochsendorf, F; Micali, G. The synergy between pharmacological regimens and dermocosmetics and its impact on adherence in acne treatment. Dermatol Res Pract; 2022; 2022, 3644720. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/35982914][PubMedCentral: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381271]
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
© The Author(s) 2025. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
Abstract
Acne and acne sequelae can have an important impact on patients’ quality of life, affecting interpersonal relationships and social functioning. Acne-induced scars (AIS) and acne-induced macular hyperpigmentation (AIH), in particular, are a major concern for patients with acne, as their management is challenging and often unsatisfactory. Retinoids are considered the mainstay of acne treatment because of their action on multiple pathogenetic factors, and there is increasing evidence that they can also improve AIS and AIH. Trifarotene, a topical retinoid with selectivity for retinoic acid receptor (RAR)-γ, has undergone an extensive clinical development programme, demonstrating its efficacy in treating facial and truncal acne and improving acne sequelae. In this article, we review the main evidence supporting the use of trifarotene in patients with acne and acne sequelae and provide place-in-therapy suggestions based on the experience of the Italian Acne Board with this drug in real-life practice. Trifarotene can be used successfully, as monotherapy or in association with other treatments, in most clinical settings of acne, but it plays an essential role in patients with existing AIS and AIH, those with a clinical or personal history of scarring and those who are predisposed to AIH. Owing to its long-term efficacy and tolerability, trifarotene is also a good option as a maintenance treatment. As with other topical retinoids, patients undergoing trifarotene therapy should be given advice on how to minimise local irritation when starting treatment.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
Details

1 “Federico II” University of Naples, Dermatology Unit, Department of Clinical Medicine and Surgery, Naples, Italy (GRID:grid.4691.a) (ISNI:0000 0001 0790 385X)
2 University of Milan, Department of Pathophysiology and Transplantation, IRCCS Ca’ Granda Foundation, Milan, Italy (GRID:grid.4708.b) (ISNI:0000 0004 1757 2822)
3 G.I.S.E.D., Italian Group of Epidemiological Studies in Dermatology, Acne and Related Dermatoses Centre, Bologna, Italy (GRID:grid.4708.b)
4 University of Catania, Dermatology Clinic, Catania, Italy (GRID:grid.8158.4) (ISNI:0000 0004 1757 1969)
5 Sapienza University of Rome, Dermatology Unit “D. Innocenzi”, Department of Medico-Surgical Sciences and Biotechnologies, Latina, Italy (GRID:grid.7841.a)
6 Laserplast Aesthetic Medicine Center, Milan, Italy (GRID:grid.7841.a)
7 Dermatological Centre in Milan, Milan, Italy (GRID:grid.7841.a)