Maintenance Acne Treatment with Topical Tazarotene after Oral Isotretinoin: Overview and Case Reports

J Clin Aesthet Dermatol. 2024;17(11–12 Suppl 1):S14–S17.

by Shanna M. Miranti, MPAS, PA-C

Ms. Miranti is with Riverchase Dermatology and Cosmetic Surgery in Naples, Florida.

FUNDING: No funding was received for this article.

DISCLOSURES: Ms. Miranti has been a speaker, consultant, and/or advisory board member for Almirall, Arcutis Biotherapeutics, Dermavant, EPI Health, Galderma, Incyte, Journey, Ortho Dermatologics, Emblation Ltd, and Verrica, and an editorial advisory board member for Dermatology Times. 

ABSTRACT: Acne is a chronic dermatologic disorder that can require long-term treatment. To prevent recurrence after oral treatment for severe acne, topical maintenance treatment is recommended; however, there is little guidance or research on maintenance regimens. This article briefly summarizes literature on oral isotretinoin and topical retinoids and presents a case series of patients who received tazarotene 0.045% lotion as maintenance following oral isotretinoin. While oral isotretinoin is efficacious, relapse/remission rates range from 0 to 69 percent depending on the definition of relapse/remission, dose, and duration of treatment/follow-up. In addition, oral isotretinoin is a known teratogen, and long-term use (>2 courses of 15-20 weeks) is not recommended. Topical treatments such as retinoids are recommended for maintenance, and some studies support that adapalene and tazarotene provide a benefit. Tazarotene 0.045% lotion is efficacious and safe, with demonstrated reductions in acne, acne-induced post-inflammatory hyperpigmentation, and melasma. In my clinic, patients with severe recalcitrant acne received once-daily oral isotretinoin for at least 20 weeks until clinically clear. On the day of last isotretinoin dose, once-daily topical tazarotene 0.045% lotion was initiated for 6 to 12 months. A total of 12 patients completed 24.3 (6.7) weeks (mean [standard deviation]) of isotretinoin (cumulative dose: 184.6 [75.1] mg/kg) and 13.0 (6.7) months of post-isotretinoin tazarotene 0.045%. No patients relapsed and all showed subjective visual improvements in acne-related scarring with topical tazarotene. None discontinued tazarotene due to adverse events. These case reports show that tazarotene 0.045% lotion may be an effective and safe treatment to prevent relapse after initial oral isotretinoin treatment. Keywords: Acne vulgaris, topical, retinoids, tazarotene, isotretinoin, maintenance, scarring 

Introduction

Acne vulgaris is a common dermatologic disorder that affects approximately 85 to 95 percent of adolescents as well as an increasing number of adults in the United States (US).^1,2 It is a chronic disease that can require treatment over months or even years.³ Acne has been shown to negatively impact quality of life and is associated with anxiety and depression,^4,5 and acne of any severity increases the risk of long-term sequelae such as scarring.^6,7

The 2024 American Academy of Dermatology treatment guidelines recommend treating mild or moderate-to-severe acne with topical monotherapy consisting of benzoyl peroxide or a retinoid, or a topical fixed-dose combination of benzoyl peroxide with a retinoid and/or an antibiotic.² Oral agents can be used for moderate-to-severe acne, including isotretinoin an antibiotic (only if combined with topical benzoyl peroxide and other topical treatment) or a combined contraceptive or spironolactone (female individuals only).² Oral antibiotics and isotretinoin, however, are not recommended for long-term use. Oral antibiotics should be prescribed for the shortest duration possible to reduce the risk of the development of bacterial resistance and oral isotretinoin has not been studied for long-term use.^2,8,9 As such, it is recommended that patients be prescribed a topical maintenance treatment once these oral treatments are complete.²

Maintenance therapy is the regular use of one or more therapeutic agents to maintain the response achieved with the initial treatment.¹⁰ There is little research on the efficacy of acne maintenance treatments. A systematic review of eight studies that assessed maintenance found that—although study designs and outcome measures differed greatly—there was some support for the use of topical treatments for maintenance after initial systemic or topical treatments.¹¹ There is also scarce guidance regarding a specific maintenance plan in terms of timing of initiation, duration, or type of therapeutic treatment.¹⁰ The American Academy of Dermatology 2024 US guidelines state only that topical treatments for maintenance can be used as monotherapy, in combination with other topical agents, or in combination with oral treatments.² Topical retinoids have specifically been described as enabling maintenance of acne clearance.² Further, clinical recommendations support the use of retinoids for maintenance therapy once oral agents are discontinued,¹² with retinoids being described as the drugs of choice for maintenance.¹³

The success of any maintenance treatment relies greatly on patient adherence, which can be negatively impacted by lack of efficacy, complicated treatment regimens, and adverse effects.¹⁴ Therefore, the objective of this case series is to present data from 12 patients from my practice who received the retinoid tazarotene 0.045% lotion as maintenance treatment following oral isotretinoin. A brief summary of the literature on oral isotretinoin and topical retinoids (including tazarotene) for acne treatment maintenance is included to provide additional context for the case series data.

Methods

In my dermatology clinic, the current practice for treating severe acne is to prescribe oral isotretinoin for at least 20 weeks and until skin is clinically clear. Once clear skin is achieved, patients begin once-daily topical tazarotene 0.045% lotion the evening of their last isotretinoin dose. The rationale for use of this lower-dose tazarotene formulation is detailed in the Discussion section. Tazarotene lotion is continued as monotherapy for at least 6 to 12 months to prevent recurrence of breakouts and to help improve the appearance of acne scarring. Patients with severe recalcitrant acne vulgaris were treated with once-daily oral isotretinoin for at least 20 weeks until they were deemed clinically clear. If a repeat course of treatment was needed, isotretinoin was given for an additional 20 weeks or until the patient was deemed clinically clear. All patients were started at 40mg isotretinoin once daily for the first 30 days. The dosage was then increased to
1mg/kg of body weight if treatment naive or 1.5–2mg/kg if this was a repeat treatment. Blood panels (complete blood count, comprehensive metabolic, lipids, and human chorionic gonadotropin [female individuals only]) were assessed once the 1mg/kg body weight dosage was reached. 

After 20 weeks, patients who achieved clinically clear skin initiated once-daily topical tazarotene 0.045% lotion monotherapy on the day of their last isotretinoin dose. A negative pregnancy test was captured on all female patients at the end of isotretinoin dosing and before the initiation of tazarotene lotion. All patients were instructed to use tazarotene in the evening and moisturizer and sunblock in the morning. Patients were also instructed not to use any other topical acne products. Follow-up visits occurred at six months and one year post-isotretinoin treatment. Photographs were taken of the face pre- and post-isotretinoin treatment and after six and 12 months of tazarotene lotion treatment to assess initial treatment response and maintenance.

Results

A total of 12 patients completed 24.3 (6.7) weeks (mean [standard deviation]) of isotretinoin treatment with a cumulative dose of 184.6 (75.1) mg/kg, and 13.0 (6.7) months of post-isotretinoin tazarotene 0.045% treatment. One patient required a repeat course of isotretinoin prior to tazarotene initiation. Patients were 17.8 (3.8) years of age and 58.3 percent were female. A total of 66.7 percent of patients were White and the remaining were Hispanic. Photographs of improvements with oral isotretinoin and post-isotretinoin tazarotene 0.045% are shown in Figure 1. No patients relapsed and all showed subjective visual improvements in acne-related scarring with topical tazarotene maintenance treatment. None discontinued tazarotene due to adverse events. 

A possible limitation of the effects observed in our case series is the short follow-up period, as relapse often occurs within 12 to 24 months of the end of treatment (see Discussion).¹⁵ Studies with a longer follow-up period might be required to confirm the initial efficacy observed in the patients included in this case series.

Discussion 

Isotretinoin is an orally active retinoic acid derivative that prevents Cutibacterium acnes proliferation and reduces sebum production, comedogenesis, and inflammation.⁷ Isotretinoin is indicated in the US for the treatment of severe recalcitrant nodular acne in nonpregnant patients aged 12 years or older who have multiple inflammatory nodules with a diameter of at least 5mm.^8,9 US treatment guidelines also recommend isotretinoin for moderate acne that is treatment-resistant or produces significant scarring or psychosocial distress.² The recommended treatment course is 15 to 20 weeks; if severe nodular acne recurs or persists at least two months after the last dose was taken, a second course of treatment can be prescribed in patients who have completed skeletal growth.^8,9 Longer-term use of oral isotretinoin has not been studied and is not recommended. Furthermore, oral isotretinoin is a known teratogen, and all patients (male or female) must enroll in the US Food and Drug Administration-mandated iPLEDGE risk evaluation and mitigation strategy program prior to use.¹⁶ 

While oral isotretinoin is efficacious in reducing acne lesions,^2,7 relapse is a known occurrence, with reported rates ranging from 0 to 69 percent. One systematic review noted that recurrence (not defined) occurred in 47 percent of the 15 reviewed studies.¹⁷ Another meta-analysis reported a recurrence range from 0 to 56.2 percent across six studies, noting that the definition of remission/relapse was either not provided or differed greatly across studies.¹⁸ In a qualitative review, six studies that did not define recurrence/relapse showed rates ranging from 10 to 69 percent (N=1,049) in patients not receiving maintenance treatment. Five studies that defined relapse (receiving anti-acne medication [i.e., a different treatment or another course of isotretinoin]) reported rates of 23 to 61 percent (N=18,230) without maintenance. In the three studies that noted a topical retinoid maintenance treatment, relapse rates were lower (2.9–9.4%; N=281).¹⁹ Three additional cross-sectional/observational studies reported relapse rates ranging from 32.7 to 37 percent, and the most frequent time to relapse ranged from 6 to 18 months.^15,20,21 One of these reports noted that 80 to 90 percent of patients who experience relapse are likely to do so within 12 to 24 months.¹⁵ The large range in recurrence rates found in the literature is likely due to differences in study designs (e.g., differing definitions of recurrence/relapse, isotretinoin doses, and duration of treatment and follow-up periods). 

Topical retinoids (tretinoin, adapalene, tazarotene, trifarotene), with their anti-inflammatory and comedolytic effects, have been a mainstay of initial acne treatment and are recommended as monotherapy or part of combination therapy for the treatment of mild or moderate-to-severe acne.^2,22,23 Additionally, some retinoids are indicated for the treatment of fine wrinkles (tretinoin, tazarotene)^24,25 and pigmentation disorders such as facial mottled hypo/hyperpigmentation associated with photodamage (tazarotene).^25–27 Some studies have shown that retinoids might also reduce acne-induced sequelae, such as scarring.^28–32 Acne-induced scarring is the result of dermal remodeling and an imbalance between matrix synthesis and matrix degradation that is coordinated via matrix metalloproteinases.³³ Most patients with acne-related scarring have a reduction in collagen.³³ Retinoids have been shown to stimulate fibroblasts to increase procollagen production in photoaged skin.^26,34,35 A potential disadvantage of topical retinoids is their association with cutaneous tolerability issues such as dryness and irritation, which can reduce adherence.^14,23 

The American Academy of Dermatology 2024 treatment guidelines state that topical therapies such as retinoids “serve as the cornerstone of acne treatment since they enable… maintenance of acne clearance.”² A systematic review from 2016 included six maintenance studies of the topical retinoids adapalene 0.1% gel and tazarotene 0.1% gel alone or in combination with other treatments. While study designs and outcome measures greatly differed across the studies, studies supported that both adapalene and tazarotene provided a benefit when used as maintenance treatment.¹¹

A relatively new lotion formulation—tazarotene 0.045% lotion (Arazlo®, Ortho Dermatologics, Bridgewater, NJ)—uses polymeric emulsion technology to provide uniform and rapid delivery of the lowest tazarotene dose commercially available. Tazarotene 0.045% lotion was developed to meet the need for an efficacious topical acne therapy with patient-friendly aesthetics, safety, and tolerability. It has demonstrated reductions in acne, acne-induced post-inflammatory hyperpigmentation (PIH), and melasma with a good safety profile.^27,36,37 Results from a Phase 2 study demonstrated that the efficacy of tazarotene lotion was comparable to tazarotene 0.1% cream, with almost half the rate of treatment-emergent adverse events.³⁸ Additionally, the polymeric emulsion lotion formulation provides rapid and sustained improvements in skin barrier function and moisturization and has cosmetic and application properties that are patient-friendly.³⁹ The low irritation potential of tazarotene 0.045% lotion has been demonstrated in head-to-head studies with other topical retinoids, in which tazarotene lotion had a significantly and numerically lower potential for irritation versus trifarotene 0.005% cream and adapalene 0.3% gel, respectively.⁴⁰ 

Conclusion

Topical tazarotene 0.045% polymeric emulsion lotion has previously demonstrated good efficacy, safety, and tolerability with acne and PIH reductions in patients with moderate-to-severe acne³⁶ and dyspigmentation reductions in patients with melasma and/or PIH.^27,37 The case reports presented here support the use of tazarotene 0.045% lotion for preventing relapse in patients with acne who have been treated with oral isotretinoin, but controlled studies with a larger sample size are needed to confirm our results.

Acknowledgments

Medical writing and editorial support were provided by Lynn M. Anderson, PhD, of Prescott Medical Communications Group, a Citrus Health Group, Inc., company (Chicago, IL), with financial support from Ortho Dermatologics. Ortho Dermatologics is a division of Bausch Health US, LLC.

References

1. Skroza N, Tolino E, Mambrin A, et al. Adult acne versus adolescent acne: a retrospective study of 1,167 patients. J Clin Aesthet Dermatol. 2018;11(1):21–25.
2. Reynolds RV, Yeung H, Cheng CE, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2024;90(5):1006.e1–1006.e30.
3. Zouboulis CC. Acne as a chronic systemic disease. Clin Dermatol. 2014;32(3):389–396.
4. Tan JK. Psychosocial impact of acne vulgaris: evaluating the evidence. Skin Therapy Lett. 2004;9(7):1–3,9.
5. Samuels DV, Rosenthal R, Lin R, et al. Acne vulgaris and risk of depression and anxiety: A meta-analytic review. J Am Acad Dermatol. 2020;83(2):532–541.
6. Dreno B, Layton A, Bettoli V, et al. Evaluation of the prevalence, risk factors, clinical characteristics, and burden of acne scars among active acne patients in Brazil, France and the USA. J Am Acad Dermatol. 2017;76(6):AB132.
7. Bellomo R, Brunner M, Tadjally E. New formulations of isotretinoin for acne treatment: expanded options and clinical implications. J Clin Aesthet Dermatol. 2021;14(12 Suppl 1):S18–S23.
8. Absorica, Absorica LD [package insert]. Cranbury, NJ: Sun Pharmaceutical Industries, Inc; 2019.
9. Accutane [package insert]. Nutley, NJ: Roche Laboratories Inc.; 2008.
10. 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:
    101–111.
11. Dressler C, Rosumeck S, Nast A. How much do we know about maintaining treatment response after successful acne therapy? Systematic review on the efficacy and safety of acne maintenance therapy. Dermatology. 2016;232(3):371–380.
12. Oge LK, Broussard A, Marshall MD. Acne vulgaris: diagnosis and treatment. Am Fam Physician. 2019;100(8):475–484.
13. Leung AK, Barankin B, Lam JM, et al. Dermatology: how to manage acne vulgaris. Drugs Context. 2021;10:2021-8-6.
14. Moradi Tuchayi S, Alexander TM, Nadkarni A, et al. Interventions to increase adherence to acne treatment. Patient Prefer Adherence. 2016;10:2091–2096.
15. Blasiak RC, Stamey CR, Burkhart CN, et al. High-dose isotretinoin treatment and the rate of retrial, relapse, and adverse effects in patients with acne vulgaris. JAMA Dermatol. 2013;149(12):1392–1398.
16. US Food and Drug Administration. iPLEDGE: Commited to Pregnancy Prevention. https://ipledgeprogram.com/#Main. Published 2021. Accessed October 31, 2023.
17. Sadeghzadeh-Bazargan A, Ghassemi M, Goodarzi A, et al. Systematic review of low-dose isotretinoin for treatment of acne vulgaris: focus on indication, dosage, regimen, efficacy, safety, satisfaction, and follow up, based on clinical studies. Dermatol Ther. 2021;34(1):e14438.
18. Tan J, Knezevic S, Boyal S, et al. Evaluation of evidence for acne remission with oral isotretinoin cumulative dosing of 120-150 mg/kg. J Cutan Med Surg. 2016;20(1):13–20.
19. Truchuelo MT, Vitale MA, Bettoli V, et al. Acne relapses and maintenance therapy: an update on definition and prevention. Sci J Clin Res Dermatol. 2017;2(1):18–27.
20. Demirci Saadet E. Investigation of relapse rate and factors affecting relapse after oral isotretinoin treatment in patients with acne vulgaris. Dermatol Ther. 2021;34(6):e15109.
21. Ibrahim S, Osman B, Awaad RM, et al. Acne vulgaris relapse in Sudanese patients treated with oral isotretinoin: rate and predictive factors. J Multidiscip Healthc. 2023;16:
    839–849.
22. Leyden J, Stein-Gold L, Weiss J. Why topical retinoids are mainstay of therapy for acne. Dermatol Ther (Heidelb). 2017;7(3):293–304.
23. Baldwin H, Webster G, Stein Gold L, et al. 50 years of topical retinoids for acne: evolution of treatment. Am J Clin Dermatol. 2021;22(3):315–327.
24. Renova [package insert]. Raritan, NJ: Ortho-Mc Neil-Janssen Pharm; 2000.
25. Avage [package insert]. Irvine, CA: Allergan; 2016.
26. Sadick N, Pannu S, Abidi Z, et al. Topical treatments for photoaged skin. J Drugs Dermatol. 2023;22(9):867–873.
27. Sadick N, Pannu S, Abidi Z, et al. Topical treatments for melasma and post-inflammatory hyperpigmentation. J Drugs Dermatol. 2023;22(11):1118–1123.
28. 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(2):275–286.
29. Dreno B, Tan J, Rivier M, et al. Adapalene 0.1%/benzoyl peroxide 2.5% gel reduces the risk of atrophic scar formation in moderate inflammatory acne: a split-face randomized controlled trial. J Eur Acad Dermatol Venereol. 2017;31(4):737–742.
30. Loss MJ, Leung S, Chien A, et al. Adapalene 0.3% gel shows efficacy for the treatment of atrophic acne scars. Dermatol Ther (Heidelb). 2018;8(2):245–257.
31. Afra TP, Razmi TM, Narang T, et al. 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(2):125–132.
32. Dréno B, Bissonnette R, Gagné-Henley A, et al. Long-term effectiveness and safety of up to 48 weeks’ treatment with topical adapalene 0.3%/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(5):725–732.
33. Fabbrocini G, Annunziata MC, D’Arco V, et al. Acne scars: pathogenesis, classification and treatment. Dermatol Res Pract. 2010;2010:893080.
34. Kang S. Photoaging and tretinoin. Dermatol Clin. 1998;16(2):357–364.
35. Griffiths CE, Russman AN, Majmudar G, et al. Restoration of collagen formation in photodamaged human skin by tretinoin (retinoic acid). N Engl J Med. 1993;329(8):
    530–535.
36. Tanghetti EA, Werschler WP, Lain E, et al. Novel polymeric lotion formulation of once-daily tazarotene (0.045%) for moderate-to-severe acne: pooled Phase 3 analysis. J Drugs Dermatol. 2020;19(3):272–279.
37. Bhatia N, Weiss JS, Sadick N, et al. Novel polymeric tazarotene 0.045% lotion for moderate-to-severe acne: pooled Phase 3 analysis by race/ethnicity. J Drugs Dermatol. 2020;19(7):727–734.
38. Tanghetti EA, Kircik LH, Green LJ, et al. A Phase 2, multicenter, double-blind, randomized, vehicle-controlled clinical study to compare the safety and efficacy of a novel tazarotene 0.045% lotion and tazarotene 0.1% cream in the treatment of moderate-to-severe acne vulgaris. J Drugs Dermatol. 2019;18(6):542.
39. Draelos Z, Tanghetti EA, Stein Gold L, et al. Tazarotene 0.045% lotion for acne: formulation, application characteristics, and clinical efficacy and safety. SKIN. 2021;5(6):s69.
40. Draelos ZD. Low irritation potential of tazarotene 0.045% lotion: head-to-head comparison to adapalene 0.3% gel and trifarotene 0.005% cream in two studies. J Dermatolog Treat. 2023;34(1):2166346.