Acne & Rosacea Treatment Therapies - Creams & Lotions

This article will explore the development and production of novel and emerging therapies for the treatment of acne and rosacea. Furthermore, mechanisms of action, efficacy, and tolerability for each will be summarized. Lastly, each treatment offers something unique in comparison to past therapies; these developments will be discussed.


Polymetric Emulsion Tretinoin 0.05% Lotion

While the role of topical tretinoin in treating acne has been well established,1 issues with patient tolerability due to initial irritation remain a challenge. Fortunately, recent advances in tretinoin formulations have taken advantage of a polymeric emulsion technology that aids in its absorption and tolerability.2 Of note, two randomized control studies evaluated the efficacy and tolerability of the polymetric emulsion tretinoin 0.05% lotion used once daily over 12 weeks.3,4 Tested individuals were ≥ 9 years old with moderate to severe acne. Inflammatory lesions showed a mean reduction of 50.9%-53.4% compared to the reduction of 40.4%-41.5% in the vehicle. Similarly, non-inflammatory lesions also showed a reduction of 47.5%-45.6% compared to the vehicle at 27.3%-31.9%. Overall, the tolerability of the formulation was excellent, with similar adverse event outcomes as the vehicle (0.51%-1.32% for treatment vs. 0.51%-0.52% vehicle). In conclusion, this formulation has demonstrated to not only be efficacious, but tolerable.

Tazarotene 0.045% Lotion

Tazarotene has been produced as a cream and more recently, a lotion. A recent phase 2 clinical trial of 210 individuals compared the efficacy and tolerability of tazarotene 0.045% lotion vs. tazarotene 0.1% cream once daily over a period of 12 weeks.5 Participants included those aged 12 and older with moderate to severe acne. The lotion was more efficacious than the cream in reducing inflammatory lesion count (60% for cream vs. 63.8% for lotion, p=0.006 compared to vehicle) as well as non-inflammatory lesion count (54.1% for cream and 56.9% for lotion, p<0.001 compared to vehicle). In terms of tolerability, the lotion fared numerically better (although not statistically significant). It should be noted, however, that this was a clinical trial with controlled measures such as which washes individuals could use. Thus, under real world circumstances the cream could potentially lead to more adverse events. Lastly, tazarotene is still contraindicated in pregnancy until further research states otherwise.6

Trifarotene Cream

Trifarotene cream, is a topical retinoid cream (50 μg/g) selective for the retinoic acid gamma receptor (RAR- γ). This formulation is not only low concentration, but very potent. Recent phase 3 studies assessed the efficacy of trifarotene on facial and truncal acne.7 In two 12-week multicentered controlled studies, over 2000 patients used trifarotene once daily for truncal acne. For the mean reduction in truncal inflammatory lesions, the first study found a reduction of 57.4% in the treatment group vs. 50.0% in the vehicle group, and study 2 showed a reduction of 51.5% in the treatment group, compared to 51.1% in the vehicle group. Non-inflammatory lesions showed similar reductions of 49.1% (vs. 40.3% in controls) in the first study and 55.2% (vs. 45.1% in controls) in the second study. This study also looked at the face, and assessed acne improvement using the Investigator Global Assessment (IGA). After 12 months, study 1 found an IGA success of 29.7%, compared to 20.0% in the vehicle group. Study 2 found an IGA success of 42.8%, compared to 25.8% in the vehicle group. In conclusion, trifarotene was significantly successful in reducing both inflammatory and non-inflammatory acne.

Benzoyl Peroxide “Stand Alone” Formulation

As over-the-counter (OTC) benzoyl peroxide (BPO) formulations have changed over the years, finding a successful combination is important for eliminating acne. One multi-center double blind study showed that an OTC 5.5% BPO with lipohydroxy acid formulation in combination with tretinoin 0.025% cream was just as efficacious as prescription clindamycin 1%- BPO 5% gel in combination with tretinoin 0.025% cream over a 12-week period.8 In the 5.5% OTC BPO formulation, inflammatory lesion counts were reduced by 68.4%, while non-inflammatory lesions were reduced by 65.2%. The prescription clindamycin 1%-BPO 5% gel had similar reductions in inflammatory lesions (63.3%) and non-inflammatory lesions (63.1%). Therefore, the “stand alone” BPO 5.5% OTC formulation is an excellent option for acne.

Microencapsulated Benzoyl Peroxide 3% and Microencapsulated Tretinoin 0.1% Cream

Encapsulated topical BPO application is a growing area of research.9 What makes this strategy unique and effective is a silica shell that wraps around the BPO and functions as a barrier between the skin and the BPO, reducing irritation while enhancing tolerability. Furthermore, as sebum slowly penetrates this barrier, it solubilizes the BPO, leading to a slower release to the sebaceous follicles. This unique technology allows the combination of BPO with ingredients that could not be combined prior. A classic example is with tretinoin, which is thought to be degraded by BPO. Now with this technology, microencapsulated BPO can be combined safely with microencapsulated tretinoin. Although this product is still in development, there are promising data.

Two multicenter, randomized, 12-week trials designated as SGT-65-04 and SGT-65-05, looked at the effects of once daily application of a combination of microencapsulated benzoyl peroxide 3% and microencapsulated tretinoin 0.1% cream.10 Adult patients achieving IGA success after 12 weeks was 38.5% and 25.4%, in SGT-65-04 and SGT-65-05 respectively, compared to 11.5% and 14.7% in controls. Furthermore, study 65-04 showed a decrease in inflammatory lesion count of 21.6 compared to the vehicle at 14.8. Similarly, study 65-05 also showed a significant reduction of 16.2 versus the vehicle at 14.1. For non-inflammatory lesions, study 65-04 saw a reduction of 29.7, versus only 19.8 in the vehicle. For study 65-05 these lesions were reduced by 24.2 in the experimental group, while the vehicle only showed a reduction of 17.4. With regards to safety, both trials demonstrated great tolerability as most skin reactions were reduced over time. Furthermore, greater than 90% of these reactions were reported as mild.

Encapsulated Benzoyl Peroxide 5% for Treatment of Rosacea

While BPO is largely avoided in rosacea due to irritation given skin sensitivity in rosacea-prone skin, this silica shell microencapsulation technology may help overcome this challenge. In a 12-week study investigating the efficacy in rosacea, 547 patients applied microencapsulated 5% BPO cream once daily.11 At week 12, 43-50% of the patients in the treatment group were clear or almost clear of papulopustular rosacea, compared to 16-26% in the vehicle group. For an additional 40 weeks (52 in total), 209 of these patients continued the treatment. At week 52, 73.2% of these patients were clear or almost clear. Tolerability was excellent, with no reported serious adverse events. Furthermore, more than 90% of individuals showed mild or no symptoms after the 52-week period.

Topical Minocycline

Topical minocycline has gained therapeutic interest due to its increased ability to penetrate the skin and limit systemic side effects.12 It has been shown that 560.21 μg/mL of 4% foam topical minocycline reaches the epidermis, compared to only 3.7 μg/mL when oral minocycline is given. Similarly, topical minocycline in the dermis was measured at 17.50 μg/mL, while only 2.3 μg/mL was measured after the use of oral minocycline. This greater penetration is believed to offer both greater efficacy and less susceptibility to antibiotic resistance. The latter is proposed to occur because of high antibiotic concentrations in the skin, making it harder for mutant strains to be representative. Conversely, concentration in the plasma was found at 1ng/mL for the topical foam, while the concentration for oral minocycline was 850 ng/mL. The lower plasma concentration found in the plasma is what is believed to lead to less side effects with the foam formulation.

The 4% foam formulation was successful in combatting acne, with a mean % reduction in inflammatory lesions of 64%-78% with daily application over a period of 12 weeks.13 This was a significant reduction in comparison to the vehicle. Furthermore, a 1.5% formulation of topical minocycline was recently approved for the treatment of rosacea. Similar treatments for acne are estimated to be approved by the end of 2020. Of note, the minocycline foam can potentially tint the skin yellow. Therefore, it is recommended to apply only a thin layer with each use.

Topical Androgen Receptor Inhibitor - Clascoterone

As androgens play a role in acne pathogenesis, researchers have begun to develop therapeutics targeting androgen receptors. Clascoterone is a topical androgen receptor inhibitor close to FDA approval. Since it is a topical, it can be used in both males and females. The goal of this therapy is to compete with DHT for receptor binding, thus inhibiting sebum production and subsequent inflammation by cytokine release.14 Recent 12-week phase 3 studies analyzed individuals applying clascoterone cream twice daily.15 Both inflammatory and non-inflammatory acne lesions demonstrated a signification reduction of 19-20 lesions, compared to reductions of 12-16 inflammatory lesions and 10-13 non-inflammatory lesions by the vehicles. Furthermore, 18-20% of individuals showed an IGA score of either 0 (clear) or 1 (almost clear). The vehicle showed only 6.5%-9% of individuals reaching these levels. With regards to safety, no adverse events were noted in these trials, and skin reactions noted were reported as mild.

Oral Tetracyclines – Sarecycline

Sarecycline, a novel oral tetracycline is now FDA approved for the treatment of acne. What makes this drug unique in comparison to other tetracyclines is its narrow spectrum of antibiotic activity, thus limiting the development of resistant strains.16 Specifically, seracycline is highly active against C. acnes and other gram positives. In comparison to other tetracyclines, however, it has low activity against many gram-negative strains, thus offering less potential to disrupt normal GI flora and confer resistance. Furthermore, sarecycline also exhibits less side effects than its tetracycline counterparts, displaying decreased photosensitivity, GI alterations, vertigo, and vaginal candidiasis.17 It should be noted while these effects are less prevalent, they are still present. Lastly, sarecycline was found to be significantly efficacious in phase III clinical trials showing a 50-52 mean % reduction of inflammatory lesions, compared to the placebo at 35%-37%.18

Table 1: Therapies & Their Effects






Polymeric emulsion tretinoin 0.05% lotion


Once daily – 12 weeks

%Inflammatory: 50.9%-53.4%

%Non-inflammatory: 47.5%-45.6%

AE: 0.51%-1.32%

Tazarotene 0.045% Lotion


Once daily – 12 weeks

%Inflammatory: 63.8%

%Non-inflammatory: 56.9%

Lotion tolerated slightly better than cream

Tazarotene 0.1% cream


Once daily – 12 weeks

%Inflammatory: 60.0%

%Non-inflammatory: 54.1%

Lotion tolerated slightly better than cream

Trifarotene Cream 50 μg/g (Trunk)


Once daily – 12 weeks

%Inflammatory: 51%-58%

%Non-inflammatory: 49%-55%


Trifarotene Cream 50 μg/g (Face)


Once daily – 12 months

%IGA success: 30%-43%


5.5% BPO, LHA, 0.025% Tretinoin


Once daily – 12 weeks

%Inflammatory: 68.4%

%Non-inflammatory: 65.2%


5.5% BPO, 1% Clindamycin, 0.025% Tretinoin


Once daily – 12 weeks

%Inflammatory: 63.3%

%Non-inflammatory: 63.1%


Microencapsulated 3% BPO & Microencapsulated 0.1% Tretinoin


Once daily – 12 weeks

IGA Success: 25%-39%

Inflammatory: 16-22 lesions

Non-inflammatory: 24-30 lesions

>90% skin reactions mild

Microencapsulated 5% BPO


Once daily – 12 weeks

73% clear or almost clear

>90% mild to no symptoms

Topical Minocycline 4% Foam


Once daily – 12 weeks

%Inflammatory: 64%-78%

Thin layer to avoid yellow tint of skin

Topical Minocycline 1.5% foam





Approved by FDA

Topical Androgen Receptor Inhibitor


Twice daily – 12 weeks

Inflammatory lesions: 19-20

Non-inflammatory lesions: 19-20

% of individuals IGA 0 or 1: 18%-20%

AE: 0%

All skin reactions reported as mild



1.5 mg/kg/day

%Inflammatory: 50%-52%

Decreased photosensitivity, GI alterations, vertigo, and vaginal candidiasis

AE: Adverse Events

%Inflammatory/%Non-inflammatory: % reduction in lesions (positive value = reduction)

Inflammatory lesions: Reduction in lesions (positive value = reduction)

Practical Tips:

  • With any acne or rosacea medication, side effects must be considered especially in pregnant individuals
  • While sarecycline may offer less side effects statistically, this does not mean they are completely void of them
  • Topical minocylines can be oily and leave individuals with yellow tinted skin, thus applying a thin layer is recommended
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