Microencapsulation technology is allowing us to mix the unmixable—benzoyl peroxide (BPO) and tretinoin. This new formulation is preserving the advantages of BPO while minimizing limitations and improving outcomes for patients with acne. Learn more about this new formulation and walk through a case scenario to see how BPO and tretinoin can now work together.
Update on the Benefits of a Microencapsulated Formulation of Benzoyl Peroxide and Tretinoin for Acne Treatment
UPDATE ON THE BENEFITS OF A MICROENCAPSULATED FORMULATION OF BENZOYL PEROXIDE AND TRETINOIN FOR ACNE TREATMENT
Acne vulgaris is a chronic, inflammatory immune-mediated skin condition that results in unsightly comedones, papules, pustules, nodules, and/or cysts on the face and other visible areas of the body.1,2 It usually begins in childhood and persists through adolescence and often into adulthood. Acne causes great distress, negatively impacting mental health and even leading to suicidal ideation. The financial burden of acne in the United States is estimated at $3 billion per year.3 Despite being one of the most common conditions treated by dermatologists and other healthcare providers, there are important treatment challenges that often lead to treatment discontinuation. These include side effects, especially with topical treatments, and noncompliance due to complicated regimens and/or lack of tolerability.3-5 Benzoyl peroxide (BP) is a foundational first-line acne treatment with important advantages. It releases free oxygen radicals, is bactericidal for Cutibacterium acnes (C. acnes) with no reported resistance, and is also comedolytic. BP is available as multiple formulations including leave-on products and washes.6 A new fixed-dose formulation of microencapsulated BP 3% and microencapsulated tretinoin 0.1% is effective in the treatment of acne and has less potential for skin irritation.7,8
BP HAS A UNIQUE MECHANISM OF ACTION THAT IS SYNERGISTIC WITH RETINOIDS
Acne results from the interaction of 4 major pathophysiologic pathways: excess sebum production, plugging of follicles with sebum and keratinocytes, colonization of follicles by the anaerobic bacteria C. acnes, and release of multiple inflammatory mediators.1,9-11 BP targets inflammatory acne with a 3-fold mechanism of action. It has sebostatic and keratolytic effects and is bactericidal for C. acnes with no resistance—an important limitation of topical antibiotics.6,12 BP also improves scarring and is effective as monotherapy and in combination with retinoids.11-13 It is available in a range of over-the-counter formulations including washes, foams, creams, and gels in strengths ranging from 2.5%-10%. Patient adherence to BP products may be limited by concentrations that cause irritation, dryness, erythema, and peeling. Certain formulations have better tolerability, and clinicians must be aware of the differences so they can select a product that optimizes patient adherence.13 Topical retinoids (eg, adapalene, tretinoin, tazarotene) are the foundation of treatment for acne of any severity. They are anti-inflammatory, comedolytic, and effective in treating precursor microcomedone lesions. They maintain lesion clearance and improve and prevent scarring.9,14-16 Retinoids are available in a variety of topical formulations including combinations and as oral medications. Adapalene 0.3% gel applied once daily for 52 weeks can cause mild or moderate local cutaneous irritation (erythema, dryness, scaling, stinging, burning).17 The synergistic efficacy of BP with adapalene is evidenced by pooled data from 3 double-blind controlled studies, in which patients were randomized to receive adapalene-BP, adapalene, BP, or vehicle once daily for 12 weeks. The combination was significantly more effective than individual components in decreasing lesion counts as early as week 1 and throughout 12 weeks.18
BP + RETINOIDS ARE THE FOUNDATIONAL TREATMENT FOR MILD, MODERATE, AND SEVERE ACNE
Acne treatment should target the known pathogenic factors, including19:
- Increased sebum production
- Hyperkeratinization of the follicular infundibulum
- Presence of C. acnes
The bactericidal properties of BP and the complementary comedolytic and anti-inflammatory effects of topical retinoids make these agents the preferred choice.19 As shown in the table below, the most recent American Academy of Dermatology (AAD) evidence-based acne treatment guidelines, published in 2017, recommend the synergistic combination of BP plus retinoids as the foundational treatment for mild, moderate, and severe acne.19,20
Table 1. First-Line and Alternation Treatment Options20
A NOVEL ENCAPSULATED FORMULATION OF BP + TRETINOIN ENHANCES EFFICACY AND TOLERABITLIY
Despite the benefits of the BP and tretinoin combination, standard formulations of tretinoin are degraded by BP; therefore, they cannot be applied at the same time.19 To overcome this limitation, a novel formulation containing a fixed-dose combination of encapsulated BP (3%) and encapsulated tretinoin (0.1%) cream was approved by the United States Food and Drug Administration (FDA) for the treatment of acne vulgaris on July 26, 2021.7 The proprietary silica-based microencapsulation technology was specifically designed to protect tretinoin from oxidative decomposition by BP, enhancing the stability of the active drug ingredients and allowing them to be combined in the same formulation. It also releases the ingredients slowly over time, decreasing the potential for skin irritation and providing a favorable efficacy and safety profile.8,21 FDA approval was based on the results of two randomized, double-blind, vehicle-controlled, multicenter phase 3 studies (NCT03761784, NCT03761810). The studies were conducted at 63 sites across the United States in a total of 858 people with moderate to severe facial acne who were 9 years of age and older. Patients were randomized to either the vehicle cream (n = 287) or the microencapsulated BP/tretinoin formulation (n = 571) once daily for 12 weeks.8,21-23 The coprimary endpoints were met in both studies. In the first trial (NCT03761784), 38.5% of patients treated with the microencapsulated BP/tretinoin formulation achieved treatment success, defined as a clear or almost clear rating at week 12 on the Investigator Global Assessment (IGA) scale, compared to 11.5% in the vehicle group. In the second study (NCT03761810), 25.4% of patients treated with the microencapsulated BP/tretinoin formulation achieved the 2-grade reduction on the IGA scale compared to 14.7% in the vehicle group. The first trial achieved a -21.6 absolute change in the baseline of inflammatory lesion count in the microencapsulated BP/tretinoin formulation group compared to -14.8 for the vehicle group at week 12. The corresponding absolute changes in the second trial were ‑16.2 in the microencapsulated BP/tretinoin formulation group and -14.1 in the vehicle group. The results for the absolute change in the non-inflammatory lesion count were similar: -29.7 in the microencapsulated BP/tretinoin formulation group and -19.8 in the vehicle group in the first trial, and -24.2 compared to -17.4, respectively, in the second trial.21-24 The new microencapsulated formulation of BP and tretinoin resulted in statistically significant and clinical meaningful improvements in IGA with corresponding reductions in both inflammatory and noninflammatory lesions and was safe and well tolerated in patients with moderate to severe acne (see figure 1).21,23
Figure 1. Benzoyl Peroxide 3% and Tretinoin 0.1%: Results from 2 Randomized Controlled Clinical Trials23
IMPROVED EFFICACY AND TOLERABILTY ENHANCES ADHERENCE TO ACNE TREATMENT
To put these ideas into practice, consider the patient case of a 19-year-old male who is a division 1 college skier struggling with facial acne. He presents to his dermatologist with papules, pustules, and open and closed comedones. He does not have truncal acne, and he states that he does not want to take an oral acne treatment. This case illustrates the importance of selecting a treatment option that optimizes efficacy, tolerability, and convenience of application to align with the personal preferences of the individual. It is important for clinicians to engage patients in shared decision-making to determine their acne severity, skin sensitivity, previous experience with acne treatments, and individual goals and preferences to develop a personalized treatment approach that optimizes efficacy and tolerability.25 In this case, the fixed-dose combination of encapsulated BP (3%) and encapsulated tretinoin (0.1%) cream is an ideal solution. The patient’s clinician should make sure he understands that he may see transient worsening of his acne shortly after starting treatment and that it may take 8 to 12 weeks before noticeable improvement.19 This is important so that he does not become discouraged and stop treatment when he does not see immediate results. He should also be followed closely and engaged in ongoing monitoring. One strategy is to ask patients to take photographs before treatment and at regular intervals to document their progress. Engaging educated patients in shared decision-making to select an effective and safe acne treatment regimen aligned to their individual needs and preferences improves outcomes, adherence, and patient satisfaction.19
- Keri JE. Acne vulgaris. Updated July 2020. Accessed November 8, 2021. https://www.merckmanuals.com/professional/dermatologic-disorders/acne-and-related-disorders/acne-vulgaris
- Bagatin E, Rocha MADD, Freitas THP, Costa CS. Treatment challenges in adult female acne and future directions. Expert Rev Clin Pharmacol. 2021;14(6):687-701.
- Habeshian KA, Cohen BA. Current issues in the treatment of acne vulgaris. Pediatrics. 2020;145(Supplement_2):S225-S230.
- Emmerich VK, Purvis CG, Feldman SR. An overview of adapalene and benzoyl peroxide once-daily topical gel as a therapeutic option for acne. Expert Opin Pharmacother. 2021;22(13):1661-1667.
- Eichenfield DZ, Sprague J, Eichenfield LF. Management of acne vulgaris: a review. JAMA. 2021;326(20):2055-2067.
- Del Rosso JQ. What is the role of benzoyl peroxide cleansers in acne management? Do they decrease propionibacterium acnes counts? Do they reduce acne lesions? J Clin Aesthet Dermatol. 2008;1(4):48-51.
- Sol-Gel Technologies and Galderma announce exclusive licenses for the commercialization of EPSOLAY® and TWYNEO® in the United States. News Release. Galderma. June 28, 2021. Accessed March 7, 2022. https://www.galderma.com/news/sol-gel-technologies-and-galderma-announce-exclusive-licenses-commercialization-epsolayr-and-1
- Sol-Gel Technologies announces FDA approval of TWYNEO®. News Release. Galderma. July 27, 2021. Accessed March 7, 2022. https://www.galderma.com/us/news/sol-gel-technologies-announces-fda-approval-twyneor
- Chien AL. Retinoids in acne management: review of current understanding, future considerations, and focus on topical treatments. J Drugs Dermatol. 2018;17(12 Suppl):s51-55.
- Cong T, Hao D, Wen X, Li XH, He G, Jiang X. From pathogenesis of acne vulgaris to anti-acne agents. Arch Dermatol Res. 2019;311(5):337-349.
- Matin T, Goodman MB. Benzoyl peroxide. In: StatPearls [Internet]. StatPearls Publishing; 2021. https://www.ncbi.nlm.nih.gov/books/NBK537220/
- Leyden JJ. The effect of benzoyl peroxide 6% wash on antibiotic-resistant propionibacterium acnes. Poster presented at: 31st Hawaii Dermatology Seminar; Wailea, Maui, Hawaii; March 3-9, 2007.
- A mainstay in treating acne: the role of benzoyl peroxide. Practical Dermatology. Accessed November 8, 2021. https://practicaldermatology.com/articles/2020-june-insert/a-mainstay-in-treating-acne-the-role-of-benzoyl-peroxide
- Leyden JJ. Current issues in antimicrobial therapy for the treatment of acne. J Eur Acad Dermatol Venereol. 2001;15 Suppl 3:51-55.
- Leyden J, Stein-Gold L, Weiss J. Why topical retinoids are mainstay of therapy for acne. Dermatol Ther (Heidelb). 2017;7(3):293-304.
- Latter G, Grice JE, Mohammed Y, Roberts MS, Benson HAE. Targeted topical delivery of retinoids in the management of acne vulgaris: current formulations and novel delivery systems. Pharmaceutics. 2019;11(10):490. doi:10.3390/pharmaceutics11100490
- Weiss JS, Thiboutot DM, Hwa J, Liu Y, Graeber M. Long-term safety and efficacy study of adapalene 0.3% gel. J Drugs Dermatol. 2008;7(6 Suppl):s24-28.
- Tan J, Gollnick HP, Loesche C, Ma YM, Gold LS. Synergistic efficacy of adapalene 0.1%-benzoyl peroxide 2.5% in the treatment of 3855 acne vulgaris patients. J Dermatolog Treat. 2011;22(4):197-205.
- Zaenglein AL. Acne vulgaris. N Engl J Med. 2018;379(14):1343-1352.
- Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74(5):945-973.e33.
- George M. Selected abstracts from MauiDerm 2021 for dermatologists. Clin Aesthet Dermatol. 2021;14(5 Suppl 1):S8–S30.
- Stocum L. Twyneo receives FDA approval for acne. Dermatology Times. July 27, 2021. Accessed March 7, 2022. https://www.dermatologytimes.com/view/twyneo-receives-fda-approval-for-acne
- Del Rosso J, Levy-Hacham O, Mizrahi O. Efficacy and safety of microencapsulated benzoyl peroxide 3% and microencapsulated tretinoin 0.1% (E-Bpo/E-Atra) in acne vulgaris: results from two randomized controlled clinical trials. SKIN The Journal of Cutaneous Medicine. 2021;5(1):s24. https://doi.org/10.25251/skin.5.supp.24
- Sol-Gel Technologies announces FDA approval of Twyneo®. GlobeNewswire. July 27, 2021. Accessed July 27, 2021. https://www.globenewswire.com/news-release/2021/07/27/2269561/0/en/Sol-Gel-Technologies-Announces-FDA-Approval-of-TWYNEO.html
- Burchett S. Is treatment of acne as simple as encouraging primary care physicians to prescribe more retinoids? J Am Acad Dermatol. 2017;76(1):e37.
In accordance with the ACCME Standards for Integrity and Independence, Global Learning Collaborative (GLC) requires that individuals in a position to control the content of an educational activity disclose all relevant financial relationships with any ineligible company. GLC mitigates all conflicts of interest to ensure independence, objectivity, balance, and scientific rigor in all its educational programs.
Hilary Baldwin, MD
The Acne Treatment and Research Center
Consulting Fees: Almirall, Cassiopea, Foamix, Galderma, Ortho Dermatologics, Sol Gel, Sun Pharm
Commercial Interest Speakers Bureau: Almirall, Cassiopea, Foamix, Galderma, Ortho Dermatologics, Sol Gel, Sun Pharma
Linda Stein Gold, MD
Director of Clinical Research
Henry Ford Hospital
Department of Dermatology
Consulting Fees: Dermavant Sciences, Inc., Incyte, Leo Pharma, Mayne Pharma, Ortho Dermatologics, Sun Pharma, Taro Pharmaceutical Industries
Commercial Interest Speakers Bureau: Leo Pharma
- Stephen Chavez has nothing to disclose.
- Cindy Davidson has nothing to disclose.
- Amanda Hilferty has nothing to disclose.
- Libby Lurwick has nothing to disclose.
- Colleen Resnick has nothing to disclose.
After participating in this educational activity, participants should be better able to:
- Recognize the clinical efficacy and tolerability of the microencapsulated formulation of benzoyl peroxide and tretinoin for the treatment of acne
- Recognize the place of benzoyl peroxide in current evidence-based treatment guidelines for mild, moderate, and severe acne
- Apply current acne treatment guidelines to select an appropriate evidence-based treatment option for patients with acne
This activity is designed to meet the educational needs of dermatologists, dermatology mid-level providers, and other HCPs specializing in acne and rosacea.
In support of improving patient care, Global Learning Collaborative (GLC) is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC) to provide continuing education for the healthcare team.
Global Learning Collaborative (GLC) designates this enduring activity for a maximum of .25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
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Peter K. Kaiser, MDPeer