INDIVIDUAL ARTICLE: Update on Combined Topical Products for Treating Acne: Leaping From Dyads

April 2024 | Volume 23 | Issue 4 | SF378083bs4 | Copyright © April 2024


Published online March 28, 2024

Naiem T. Issa MD PhDa, Leon Kircik MDb

aForefront Dermatology, Vienna, VA; Issa Research & Consulting, LLC, Springfield, VA; Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL; Department of Dermatology, George Washington University School of Medicine & Health Sciences, Washington, DC 
bIcahn School of Medicine at Mount Sinai, New York, NY; Indiana University Medical Center, Indianapolis, IN; Physicians Skin Care, PLLC Louisville, KY; DermResearch, PLLC Louisville, KY; Skin Sciences, PLLC Louisville, KY

Tretinoin has also been successfully combined with BPO via microencapsulation technology.34 A formulation containing encapsulated BPO 3%/encapsulated tretinoin 0.1% (E-BPO/T) cream has been investigated in 571 subjects 9 years of age or older with moderate to severe acne.35 Once-daily application of E-BPO/T was significantly superior to the vehicle with respect to changes from baseline in both inflammatory and noninflammatory lesion counts across both parallel, randomized, controlled trials.35

Clindamycin-Tretinoin Combination
Clindamycin has also been combined with tretinoin in a gel formulation (CDP 1.2%/tretinoin 0.025%).36 A pooled analysis of 4550 subjects across three pivotal trials showed CDP/tretinoin to be effective in treating both inflammatory and non-inflammatory acne lesions as early as 2 weeks into treatment.37,38 The formulation is also unique in that it contains a combination of solubilized and crystalline retinoid that allows for both rapid and slower prolonged follicular penetration, leading to deeper penetration of clindamycin.37 Furthermore, CDP/tretinoin exhibited greater efficacy compared to each monad.39 A post hoc analysis in 797 subjects from the parallel 12-week pivotal trials also showed that acne subjects with Fitzpatrick skin types IV-VI exhibited efficacy and tolerability that was comparable to subjects with Fitzpatrick skin types I-III.40

As clindamycin is being used unopposed (ie, no BPO is used in conjunction), there is a significant risk of developing antibiotic resistance in C. acnes.41 In fact, antibiotic resistance rates across the globe continue to rise, ranging from 50-93% in European countries with many countries reporting antibiotic resistance in more than 50% of C. acnes strains.42,43 Given that antibiotics are the cornerstone of acne treatment and that millions of individuals receive antibiotics worldwide for acne annually, antibiotic stewardship must be embraced to maintain the efficacy of current and future treatments. 

Tolerability
While the aforementioned topical dyads exhibit largely similar efficacies in the treatment of acne, they do differ in tolerability. This is important in treatment decision-making as current guidelines recommend BPO-containing dyads over those that do not contain BPO due to risk of developing antibiotic resistance.8 Few studies directly assessed the tolerability of these dyads against each other, however. Gonzalez et al performed a randomized, single-blind, split-face study comparing the tolerability profiles of clindamycin 1%/BPO 2.5% gel versus adapalene 0.1%/BPO 2.5% gel in 45 subjects over 2 weeks and found that clindamycin/BPO was better tolerated than adapalene/BPO.44 Bhatia et al found adapalene 0.3%/BPO 2.5% gel to be less tolerable than clindamycin-BPO 3.75% gel in a 21-day split-face study in healthy volunteers with no apparent facial redness or dryness.45 Goreshi et al performed a double-blind, randomized split-faced study comparing the tolerability of clindamycin 1.2%/tretinoin 0.025% to adapalene 0.1%/BPO 2.5% applied daily for 21 days.46 Subjects reported significantly less burning, stinging, and pruritus with adapalene 0.1%/BPO 2.5% thus demonstrating significantly less skin irritancy compared to clindamycin 1.2%/tretinoin 0.025%. Aschoff et al similarly showed adapalene 0.1%/BPO 2.5% to be better tolerated compared to clindamycin 1.2%/tretinoin 0.025% in a 3-week blinded, randomized, split-faced study in 22 subjects with mild to moderate acne vulgaris.47 To date, no studies have been conducted comparing the tolerability of tretinoin 0.1%/BPO 0.3% cream to the other dyads. 

IDP-126: The First-In-Class Triple Combination Topical Therapeutic
In 2023, a novel first-in-class triple combination topical gel - IDP-126 - was approved by the FDA for once-daily application for the treatment of acne in patients aged 12 and older.48 While several BPO/adapalene or BPO/clindamycin dyad formulations have been approved, IDP-126 is the first topical product to incorporate three bioactive pharmaceutical agents. IDP-126 contains fixed-dose clindamycin phosphate 1.2%, BPO 3.1%, and adapalene 0.15% in a polymeric mesh gel with micronized particles of BPO and adapalene. Micronized BPO and adapalene allow for a stable combination of ingredients and smaller particle sizes which more effectively penetrate the pilosebaceous unit.49 The polymeric mesh allows for even distribution of the active agents on the skin utilizing a vehicle formulated with an aqueous gel without alcohol, occluding agents, surfactants, or preservatives while containing the hydrating humectant propylene glycol.50 Furthermore, the polymeric mesh vehicle with micronized ingredients may provide better tolerability, which has been an obstacle with the prior topical dyad combinations.51,52 

Once daily application of IDP-126 was recently studied in a phase 2 randomized, double-blind, parallel-group, vehicle-controlled clinical trial in 741 subjects aged >= 9 years with moderate-to-severe acne over 12 weeks.53 Acne severity was graded using the Evaluator's Global Severity Score (EGSS) with scores of 3 and 4 corresponding to moderate and severe acne, respectively. Subjects were equally randomized into one of five treatment groups: IDP-126, vehicle, and one of three component dyads formulated with the same active drug concentration and within the same vehicle as IDP-126. The dyads are as follows: (1) BPO 3.1%/adapalene 0.15% gel, (2) clindamycin phosphate 1.2%/BPO 3.1% gel, and (3) clindamycin phosphate 1.2%/adapalene 0.15% gel. Co-primary endpoints were the percentage of participants achieving treatment success at week 12 and the absolute changes from baseline to week 12 in inflammatory and non-inflammatory lesion counts. Treatment success was defined as a >= 2-grade reduction from baseline in EGSS and a score of 0 (clear) or 1 (almost clear). Patient-reported quality-of-life outcomes were also secondarily assessed through the Acne-Specific Quality of Life (Acne-QoL) questionnaire administered at baseline and week 12.

At week 12, 52.5% of subjects with IDP-126 achieved treatment success which is significantly greater than the three dyad gels (range 27.8-30.5%) and vehicle gel (8.1%). Success in the IDP-126 group was 1.7-1.8 times greater than with the component dyads, suggesting potential further improvement with the triple combination over the different dual combinations.18 The same trend in superiority was observed in absolute mean reductions in inflammatory and noninflammatory lesions from baseline to week 12. Furthermore, treatment success, absolute mean reductions in inflammatory and noninflammatory lesion counts, and least-squares mean percent changes in acne lesion counts were all significantly greater in the IDP-126 group compared to vehicle as early as weeks 4, 2, and 2, respectively, suggesting a fast onset of action. With respect to patient-reported QoL, Acne-QoL scores at week 12 were numerically greater for the IDP-126 group vs all three dyad treatment groups and vehicle across all domains. 

Subsequent phase 3 studies assessed the efficacy and safety of IDP-126 compared to vehicle.54 Across the two multicenter, randomized, double-blind, parallel-group, vehicle-controlled studies, a total of 363 patients aged 9 and older with moderate or severe acne (EGSS 3 or 4) were enrolled and randomized 2:1 to once-daily IDP-126 or vehicle gel. Co-primary and secondary efficacy endpoints were the same as in the phase 2 study noted above. IDP-126 was superior to vehicle gel for all co-primary and secondary endpoints across both studies. Treatment success (EGSS 0 or 1 with >= 2-point reduction) at week 12 was achieved by 49.6% and 50.5% in the IDP-126 group compared to 24.9% and 20.5% in the vehicle group (studies 1 and 2, respectively). A significantly greater absolute mean reduction, as well as least-squares, mean percent change in inflammatory and noninflammatory lesions was seen in the IDP-126 group versus the vehicle group at week 12. IDP-126 also exhibited significantly greater percent changes in lesion reduction as early as week 4. These results are consistent with those from the phase 2 study noted above. Moreover, when contextualizing these results with the 10- and 12-week phase 3 trials of other commercially available dyads, IDP-126 exhibited the greatest numeric mean percent reductions in inflammatory and noninflammatory lesions. As no head-to-head parallel group studies were conducted, no direct comparisons can currently be made, however. A post-hoc analysis of pooled phase 3 data also showed meaningful improvements in quality-of-life measures that correlated with EGSS scores.55 Furthermore, a recent meta-analysis assessing pharmacological treatments for acne placed the triple combination as the second most efficacious treatment for total lesion reduction after isotretinoin.56 

IDP-126 was also well tolerated. There was a low rate of discontinuation (<4%) due to treatment-emergent adverse events (TEAE), and no participants experienced serious AEs. Regarding safety and tolerability, there were early but transient increases in severity for burning, stinging, itching, erythema, and scaling from baseline to week 2 but were considered mild (score below 1) on average. The phase 2 tolerability data also showed that IDP-126 may have a better tolerability profile compared with the BPO/adapalene dyad.53 In addition, a post hoc analysis further demonstrated that skin of color patients tolerated IDP-126 well and experienced improvement in erythema without increases in hyperpigmentation or hypopigmentation.57 
 

DISCUSSION

Acne vulgaris continues to be a pervasive dermatologic condition affecting the quality of life for billions of people worldwide. Advances in drug formulations and vehicle technologies over the last decade have allowed for the combination of active molecules that traditionally would destabilize each other thereby rendering them ineffective. These combinations have allowed for an increase in efficacy and a reduction in the development of antibiotic resistance in those formulations that contain BPO.58 Furthermore, combination topicals have resulted in greater compliance with treatment by patients given lower dosing frequencies and the reduced number of topicals needed to use in daily acne treatment regimens.59

Tolerability is also critical for patient compliance. While the vehicle composition and formulation are critical for the tolerability of topical treatments, as evident by the polymeric mesh technology, it is thought that clindamycin exhibits anti-inflammatory effects that may optimize tolerability. Split-face studies comparing topical dyads have demonstrated that clindamycin phosphate/BPO is less irritating than adapalene/BPO.44,60,61 A meta-analysis by Stuart et al also showed that the odds of patient withdrawal due to adverse effects was lower when clindamycin was combined with BPO compared to BPO alone or BPO combined with adapalene.51  

CONCLUSION

Topical drug formulation technologies have advanced and allowed for the development of topical acne treatments that contain two or three formerly incompatible active molecules thus allowing for simultaneously targeting multiple pathophysiologic mechanisms underlying acne vulgaris. These formulations allow for synergistic efficacy, reduced application frequency, reduced number of topicals utilized in daily acne treatment routines, and improved tolerability. These factors comprehensively aid in the reduction of antibiotic resistance with acne therapy while improving patient compliance with treatment regimens.

DISCLOSURES

Leon Kircik MD has served as either an investigator, consultant, speaker, or advisory board member for Allergan, Allmirall, Biofrontera, Galderma, L'Oreal, Mayne Pharma, Ortho Dermatologics, and SUN Pharma. Naiem T. Issa has received funding from the following entities either as a speaker, consultant, advisor, or investigator Bristol Myers Squibb, Castle Biosciences, Dermavant Sciences, DermTech, Galderma, LEO Pharma, Lilly, National Eczema Association, Ortho Dermatologics, Pfizer, RBC Consultants, Verrica Pharmaceuticals, and WebMD.

REFERENCES

  1. Zouboulis CC, Eady A, Philpott M, et al. What is the pathogenesis of acne? Exp Dermatol. 2005;14(2):143-152. 
  2. Williams HC, Dellavalle RP, Garner S. Acne vulgaris. Lancet. 2012;379(9813):361- 372. 
  3. Thiboutot D, Gollnick H, Bettoli V, et al. New insights into the management of acne: an update from the Global Alliance to Improve Outcomes in Acne group. J Am Acad Dermatol. 2009;60(5 Suppl):S1-50. 
  4. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74(5):945-73.e33. 
  5. Okamoto K, Kanayama S, Ikeda F, et al. Broad spectrum in vitro microbicidal activity of benzoyl peroxide against microorganisms related to cutaneous diseases. J Dermatol. 2021;48(4):551-555. 
  6. Baldwin H, Elewski B, Hougeir F, et al. Sixty years of benzoyl peroxide use in dermatology. J Drugs Dermatol. 2023;22(1):54-59. 
  7. Thiboutot DM, Dreno 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(2 Suppl 1):S1-S23.e1. 
  8. Nast A, Dreno 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(8):1261-1268. 
  9. Martin B, Meunier C, Montels D, Watts O. Chemical stability of adapalene and tretinoin when combined with benzoyl peroxide in presence and in absence of visible light and ultraviolet radiation. Br J Dermatol. 1998;139 Suppl 52:8-11. 
  10. Baldwin HE. Tricks for improving compliance with acne therapy. Dermatol Ther. 2006;19(4):224-236. 
  11. Lee IA, Maibach HI. Pharmionics in dermatology: a review of topical medication adherence. Am J Clin Dermatol. 2006;7(4):231-236.
  12. Stein Gold L, Kwong P, Draelos Z, et al. Impact of topical vehicles and cutaneous delivery technologies on patient adherence and treatment outcomes in acne and Rosacea. J Clin Aesthet Dermatol. 2023;16(5):26-34. 
  13. Vyas A, Kumar Sonker A, Gidwani B. Carrier-based drug delivery system for treatment of acne. ScientificWorldJournal. 2014;2014:276260. 
  14. Kircik LH. Microsphere technology: hype or help? J Clin Aesthet Dermatol. 2011;4(5):27-31. 
  15. Garg T. Current nanotechnological approaches for an effective delivery of bio-active drug molecules in the treatment of acne. Artif Cells Nanomed Biotechnol. 2016;44(1):98-105. 
  16. Ciriminna R, Sciortino M, Alonzo G, Schrijver A de, Pagliaro M. From molecules to systems: sol-gel microencapsulation in silica-based materials. Chem Rev. 2011;111(2):765-789. 
  17. Rosso JD, Harper J, Pillai R, Moore R. Tretinoin photostability: comparison of micronized tretinoin gel 0.05% and tretinoin gel 0.025% following exposure to fluorescent and solar light. J Clin Aesthet Dermatol. 2013;6(2):25-28. 
  18. Kircik LH. Synergy and its clinical relevance in topical acne therapy. J Clin Aesthet Dermatol. 2011;4(11):30-33. 
  19. Warner GT, Plosker GL. Clindamycin/benzoyl peroxide gel: a review of its use in the management of acne. Am J Clin Dermatol. 2002;3(5):349-360. 
  20. Xu JH, Lu QJ, Huang JH, et al. A multicentre, randomized, single-blind comparison of topical clindamycin 1%/benzoyl peroxide 5% once-daily gel versus clindamycin 1% twice-daily gel in the treatment of mild to moderate acne vulgaris in Chinese patients. J Eur Acad Dermatol Venereol. 2016;30(7):1176-1182. 
  21. Pariser DM, Rich P, Cook-Bolden FE, Korotzer A. An aqueous gel fixed combination of clindamycin phosphate 1.2% and benzoyl peroxide 3.75% for the once-daily treatment of moderate to severe acne vulgaris. J Drugs Dermatol. 2014;13(9):1083-1089. 
  22. Cook-Bolden FE. Efficacy and tolerability of a fixed combination of clindamycin phosphate (1.2%) and benzoyl peroxide (3.75%) aqueous gel in moderate or severe adolescent acne vulgaris. J Clin Aesthet Dermatol. 2015;8(5):28-32. 
  23. Cook-Bolden FE. Treatment of moderate to severe acne vulgaris in a Hispanic population: a post-hoc analysis of efficacy and tolerability of clindamycin phosphate 1.2%/benzoyl peroxide 2.5% gel. J Drugs Dermatol. 2012;11(4):455- 459. 
  24. US Food and Drug Administration. Drugs@FDA: FDA-approved drugs. https:// www.accessdata.fda.gov/drugsatfda_docs/label/2010/050819s003lbl.pdf. Accessed 25 Aug 2021. 
  25. Eichenfield LF, Krakowski AC. Moderate to severe acne in adolescents with skin of color: benefits of a fixed combination clindamycin phosphate 1.2% and benzoyl peroxide 2.5% aqueous gel. J Drugs Dermatol. 2012;11(7):818-824. 
  26. Gollnick HPM, Draelos Z, Glenn MJ, et al. Adapalene-benzoyl peroxide, a unique fixed-dose combination topical gel for the treatment of acne vulgaris: a transatlantic, randomized, double-blind, controlled study in 1670 patients. Br J Dermatol. 2009;161(5):1180-1189. 
  27. Feldman SR, Tan J, Poulin Y, Dirschka T, Kerrouche N, Manna V. The efficacy of adapalene-benzoyl peroxide combination increases with number of acne lesions. J Am Acad Dermatol. 2011;64(6):1085-1091. 
  28. Tan J, Gollnick HPM, 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. 
  29. Leyden JJ, Preston N, Osborn C, Gottschalk RW. In-vivo effectiveness of adapalene 0.1%/benzoyl peroxide 2.5% gel on antibiotic-sensitive and resistant Propionibacterium acnes. J Clin Aesthet Dermatol. 2011;4(5):22-26. 
  30. Stein Gold L, Weiss J, Rueda MJ, Liu H, Tanghetti E. Moderate and severe inflammatory acne vulgaris effectively treated with single-agent therapy by a new fixed-dose combination adapalene 0.3 %/benzoyl peroxide 2.5 %gel: A randomized, double-blind, parallel-group, controlled study. Am J Clin Dermatol. 2016;17(3):293-303.
  31. Stein Gold L, Werschler WP, Mohawk J. Adapalene/benzoyl peroxide gel 0.3%/2.5%: Effective acne therapy regardless of age or gender. J Drugs Dermatol. 2017;16(6):582-589. 
  32. DuBois J, Ong GCW, Petkar G, et al. Patient-reported outcomes in acne patients with skin of color using adapalene 0.3%-benzoyl peroxide 2.5%: A prospective real-world study. J Drugs Dermatol. 2019;18(5):514. 
  33. Alexis AF, Cook-Bolden FE, York JP. Adapalene/benzoyl peroxide gel 0.3%/2.5%: A safe and effective acne therapy in all skin phototypes. J Drugs Dermatol. 2017;16(6):574-581. 
  34. Green LJ, Bhatia ND, Toledano O, et al. Silica-based microencapsulation used in topical dermatologic applications. Arch Derm Res. 2023;315(10):2787-2793. 
  35. Del Rosso J, Sugarman J, Green L, et al. Efficacy and safety of microencapsulated benzoyl peroxide and microencapsulated tretinoin for the treatment of acne vulgaris: Results from two phase 3 double-blind, randomized, vehicle-controlled studies. J Am Acad Dermatol. 2023;89(4):719- 727. 
  36. US Food and Drug Administration. Drugs@FDA: FDA-approved drugs. https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/050802lbl.pdf. Accessed 30 Nov 2023. 
  37. Ochsendorf F. Clindamycin phosphate 1.2% / tretinoin 0.025%: a novel fixed-dose combination treatment for acne vulgaris. J Eur Acad Dermatol Venereol. 2015;29 Suppl 5:8-13. 
  38. Dreno B, Bettoli V, Ochsendorf F, et al. Efficacy and safety of clindamycin phosphate 1.2%/tretinoin 0.025% formulation for the treatment of acne vulgaris: pooled analysis of data from three randomised, double-blind, parallel-group, phase III studies. Eur J Dermatol. 2014;24(2):201-209. 
  39. Jarratt MT, Brundage T. Efficacy and safety of clindamycin-tretinoin gel versus clindamycin or tretinoin alone in acne vulgaris: a randomized, double-blind, vehicle-controlled study. J Drugs Dermatol. 2012;11(3):318-326. 
  40. Callender VD. Fitzpatrick skin types and clindamycin phosphate 1.2%/benzoyl peroxide gel: efficacy and tolerability of treatment in moderate to severe acne. J Drugs Dermatol. 2012;11(5):643-648. 
  41. Platsidaki E, Dessinioti C. Recent Advances in Understanding Propionibacterium Acnes ( Cutibacterium Acnes) in Acne. F1000Res.; 2018. 
  42. Ross JI, Snelling AM, Carnegie E, et al. Antibiotic-resistant acne: lessons from Europe. Br J Dermatol. 2003;148(3):467-478. 
  43. Walsh TR, Efthimiou J, Dreno B. Systematic review of antibiotic resistance in acne: an increasing topical and oral threat. Lancet Infect Dis. 2016;16(3):e23- 33. 
  44. Gonzalez P, Vila R, Cirigliano M. The tolerability profile of clindamycin 1%/ benzoyl peroxide 5% gel vs. adapalene 0.1%/benzoyl peroxide 2.5% gel for facial acne: results of a randomized, single-blind, split-face study. J Cosmet Dermatol. 2012;11(4):251-260. 
  45. Bhatia N, Bhatt V, Martin G, Pillai R. Two randomized, double-blind, split-face studies to compare the irritation potential of two topical acne fixed combinations over a 21-day treatment period. J Drugs Dermatol. 2016;15(6):721-726. 
  46. Goreshi R, Samrao A, Ehst BD. A double-blind, randomized, bilateral comparison of skin irritancy following application of the combination acne products clindamycin/tretinoin and benzoyl peroxide/adapalene. J Drugs Dermatol. 2012;11(12):1422-1426. 
  47. Aschoff R, Moller S, Haase R, Kuske M. Tolerability and Efficacy of Clindamycin/Tretinoin versus Adapalene/Benzoyl Peroxide in the Treatment of Acne Vulgaris. J Drugs Dermatol. 2021;20(3):295-301.
  48. FDA Approves Cabtreo (Clindamycin Phosphate, Adapalene and Benzoyl Peroxide) Topical Gel for the Treatment of Acne Vulgaris in Patients Twelve Years of Age and Older. Bausch Health Companies Inc. Press release. Accessed December 01, 2023. https://ir.bauschhealth.com/news-releases/2023/10-20-2023.
  49. Baldwin H, Webster G, Stein Gold L, Callender V, Cook-Bolden FE, Guenin E. Coli 50 years of topical retinoids for acne: Evolution of treatment. Am J Clin Dermatol. 2021;22(3):315-327. 
  50. Kircik LH, Draelos ZD, Berson DS. Polymeric emulsion technology applied to tretinoin. J Drugs Dermatol. 2019;18(4):s148-154.
  51. Stuart B, Maund E, Wilcox C, et al. Topical preparations for the treatment of mild-to-moderate acne vulgaris: systematic review and network meta-analysis. Br J Dermatol. 2021;185(3):512-525.
  52. Del Rosso JQ, Tanghetti E. The clinical impact of vehicle technology using a patented formulation of benzoyl peroxide 5%/clindamycin 1% gel: comparative assessments of skin tolerability and evaluation of combination use with a topical retinoid. J Drugs Dermatol. 2006;5(2):160-164.
  53. Stein Gold L, Baldwin H, Kircik LH, et al. Efficacy and safety of a fixed-dose clindamycin phosphate 1.2%, benzoyl peroxide 3.1%, and adapalene 0.15%gel for moderate-to-severe acne: A randomized phase II study of the first triple-combination drug. Am J Clin Dermatol. 2022;23(1):93-104.
  54. Stein Gold L, Lain E, Del Rosso JQ, et al. Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% gel for moderate-to-severe acne: Efficacy and safety results from two randomized phase 3 trials. J Am Acad Dermatol. 2023;89(5):927-935.
  55. Gold LS, Harding G, Borroto D, et al. Post-hoc exploratory pooled analysis of the impact of IDP-126 gel on QoL in moderate-to-severe acne. J Drugs Dermatol. 2023;22(10):1033-1039.
  56. Huang CY, Chang IJ, Bolick N, et al. Comparative efficacy of pharmacological treatments for acne vulgaris: A network meta-analysis of 221 randomized controlled trials. Ann Fam Med. 2023;21(4):358-369.
  57. Callender V, Cook-Bolden F, Kircik L. Safety and tolerability of fixed-dose clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% gel in Black participants with acne. In: Poster Presented at the 2023 Society of Dermatology Physician Assistants Fall Conference.
  58. Karadag AS, Aslan Kayıran M, Wu CY, Chen W, Parish LC. Antibiotic resistance in acne: changes, consequences and concerns. J Eur Acad Dermatol Venereol. 2021;35(1):73-78.
  59. Yentzer BA, Ade RA, Fountain JM, et al. Simplifying regimens promotes greater adherence and outcomes with topical acne medications: a randomized controlled trial. Cutis. 2010;86(2):103-108.
  60. Ting, W., Randomized, observer-blind, split-face study to compare the irritation potential of 2 topical acne formulations over a 14-day treatment period. Cutis. 2012;90(2):91-96.
  61. Green L, Cirigliano M, Gwazdauskas JA, Gonzalez P. The tolerability profile of clindamycin 1%/benzoyl peroxide 5% gel vs. Adapalene 0.1%/benzoyl peroxide 2.5% gel for facial acne: Results of two randomized, single-blind, split-face studies. J Clin Aesthet Dermatol. 2012;5(5):16-24.

AUTHOR CORRESPONDENCE

Leon Kircik MD wedoderm@yahoo.com
Close Menu