Topical Acne Therapy: Current and Advanced Options for Optimizing Adherence

J. K. L. Tan, MD, FRCPC
Department of Medicine, University of Western Ontario, London, ON, Canada
Windsor Clinical Research Inc., Windsor, ON, Canada

Introduction

Acne is the most common skin disorder treated by physicians, affecting about 85% of individuals between the ages of 12-24 years.¹ Adult-onset acne is increasingly common with presentation in patients beyond their teenage years. Topical treatment is the mainstay for mild disease and adjunctive to oral or hormonal therapy for moderate acne. However, patients often consider topical medications to be time-consuming and inconvenient to use, irritating to the skin, and less potent than systemic therapy. These factors can engender nonadherent behaviour and treatment dissatisfaction. This article explores recent formulary advances and offers clinical strategies that can encourage adherence and improve treatment outcomes.

Prevalence

Adolescent Acne

• The primary cause is attributable to increased hormonal activity that triggers sebum production.
• Onset ranges between ages 10-13 years, generally resolving by the early 20s.
• Areas of frequent involvement include the cheeks, chin, forehead, and nose. In severe cases, the back, chest, neck, shoulder, and upper arms can be affected.
• Severe disease is more prevalent among males.
• Teenagers and adult females are particularly susceptible to the negative psychosocial impacts of acne, which can result in low self-esteem and self-confidence, an inferior body image, and avoidance of social interactions.

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Post-adolescent Acne

• Evidence suggests that adult/mature acne is increasing in prevalence, and with this trend, a growing concern regarding the potential for serious psychosocial concomitants (e.g., depression and anxiety) in affected individuals.²
• There are two generally accepted types:
  1. Persistent acne refers to acne that does not clear by the mid-20s. Lesions commonly develop on the lower face.
  2. Late-onset acne may be caused by hormones, stress, bacterial colonization, and cosmetics. As with persistent acne, the lower face is most frequently affected, but lesions can also occur on the back and chest.
• This variant is more prevalent in women; it frequently affects perioral regions (i.e., the chin, around the mouth, and along the jaw line) and flares premenses.

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Treatment Selection

• Accessibility of anatomical site for application
• Ease of application
• Efficacy and rapid onset of action
• Regimen simplicity
• Tolerability
• Convenience
• Cosmetic acceptability
• Cost

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Topical Acne Agents

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Therapeutic Advances

Combination Therapy with BPO

• led tretinoid derivatives that are photostable and more chemically stable, even in the presence of an oxidizing agent, such as BPO.
• permitted the use of tretinoin gel microsphere (TGM) and adapalene in the morning, or directly before or after BPO application.
• decreased the emergence of bacterial resistance due to the addition of BPO to topical antibiotic agents, and the use of BPO with long-term oral antibiotics.

Vehicle Technology in Topical Acne Preparations⁴

• Many new topical acne formulations have aqueous-based gel vehicle delivery systems that do not contain alcohol and are suitable for use in all skin types.
• A once-daily formulation of clindamycin in a foam vehicle improves absorption and cosmetic acceptability, and facilitates ease of use, especially over larger or hair-bearing areas.
• Clindamycin 1% + BP5% gel formulation includes both glycerin (humectant) and dimethicone (emollient) to reduce both epidermal barrier impairment and cutaneous irritation, and increase hydration.

Microsphere Technology and Pump Delivery System

• less irritation due to the slow release of tretinoin from the microspheres in to the epidermis.
• improved photostability, allowing for morning use.
• improved ease of use. TGM is a water-based gel that can be applied to the face immediately after washing.
• an innovative dispensing system (i.e., a dual chambered pump dispenser that releases the correct and consistent pea-sized amount for full face application).
  • Controlled dispensing of tretinoin limits irritation, which can encourage medication adherence.
  • The pump system allows simple dosing instructions (e.g., apply 2 pumps to the affected facial area).
  • A multicenter trial of 544 acne patients who were dissatisfied with their current treatment used TGM for 12 weeks. Most patients (82.3%) rated the pump as an excellent or very good method of dispensing acne medication. The tretinoin pump system significantly increased adherence, quality of life, and treatment satisfaction for study patients.⁶

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The Treatment Horizon

Novel combinations and new uses of existing agents are expanding the spectrum of topical antiacne therapies.

Adapalene + BPO

• A novel once-daily acne treatment combining adapalene with BPO was US FDA-approved in January 2009.
• Multiple pathogenic factors are targeted. Adapalene modulates cellular differentiation, keratinization, and inflammation; BPO has bactericidal and keratolytic effects.

Azelaic Acid

• Due tits antibacterial, anti-inflammatory, keratolytic, and comedolytic effects, azelaic acid 15% gel has been used successfully alone or in combination with other medications to treat mild-to-moderate acne.
• It also reduces post-inflammatory hyperpigmentation, once acne lesions heal.

Dapsone

• Dapsone, an antibacterial agent, was US FDA-approved in 2008 for the treatment of moderate-to-severe acne.
• Studies with dapsone 5% gel showed significant reductions in acne lesions following 4 weeks of therapy.⁷

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Treatment Adherence

1. Difficulties with the patient-physician relationship (i.e., miscommunication, lack of dialogue, and patient misconception of benefits and risks of treatment).

• The treatment plan, rate of improvement, and side-effects may be inadequately explained to patients.
• Patients misunderstand physician instructions.

2. Treatment-related issues:

• The most common reasons include forgetfulness, side-effects, did not feel the need, and inconvenience.
• Adherence is also compromised by the lag time to visible effect, the complexity of treatment regimens, and the desire to incorporate cosmetics, such as foundations, moisturizers, and sunscreens.

Pharmacists Offer Frontline Support

Pharmacists are crucial advocates in communicating therapeutic objectives to patients, educating them on both acne and medications, and encouraging adherence through:

• reinforcing the aims of initial and long-term strategies.
• assisting to establish realistic treatment expectations, including clinically relevant improvement, which is approximately 4-6 weeks for most topical therapies.
• counselling on aggravating factors, proper medication use, and potential adverse effects.
• emphasizing to patients that overuse can amplify skin irritation and underuse can reduce product efficacy.
• understanding that even mild acne can have a profound emotional impact on affected patients.
• implementing the prescribing physician's vehicle recommendations. In particular, avoiding substitution of the pump dispenser for the tube, in order to gain patient adherence and treatment satisfaction.

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Tips for Acne Management

• Select aqueous over alcohol vehicles to reduce irritation.
• Frequency and duration of application may be adjusted to reduce the potential for dryness and irritation (e.g., initiate once-daily treatment after dinner; progressively increase duration as patient tolerance permits).
• Provide descriptive estimates of amounts to apply (e.g., pea-size amount of gel teach of the four facial regions: forehead, each cheek, central face).
• Advise patients to apply topical medications to the entire affected area and not just the acne lesions.
• Use simple skin care regimens:
  • Patients who do not use foundation or sunscreen can apply topical agents in the morning and evening.
  • If patients use foundation and sunblock, apply medication in the evening only or apply a clindamycin product with SPF 15 in the morning.
  • Suggest using gentle cleansers to avoid compounding irritation and dryness.
  • Recommend using non-comedogenic foundations, water-based cleansers, and oil-free moisturizers.

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Conclusion

An interplay of multiple factors contributes to the successful outcome of topical acne treatment. The appropriate selection of medications and vehicles should be patient-specific and take into account efficacy, tolerability, and convenience, as well as individual preferences. Furthermore, pharmacologic initiatives aimed at optimizing acne management must be accompanied by patient education. Advances in topical acne formulations, active agents, and vehicles hold the promise of improved outcomes with reduced adverse effects, greater tolerability, and dosing simplicity.

References

1. Krowchuk DP, et al. Adolesc Med 12(2):vii, 355-74 (2001 Jun).
2. Knaggs HE, et al. Int J Cosmet Sci 26(3):129-38 (2004 Jun).
3. Kircik L. Cutis 80(1 Suppl):10-4 (2007 Jul).
4. Skotnicki-Grant S. Skin Therapy Lett FP 4(3):4-5 (2008 Jun).
5. Berger R, et al. Cutis 80(2):152-7 (2007 Aug).
6. Eichenfield LF, et al. J Drugs Dermatol 7(12):1129-36 (2008 Dec).
7. Del Rosso JQ. Cutis 80(5):400-10 (2007 Nov).
8. Renzi C, et al. Arch Dermatol 138(3):337-42 (2002 Mar).

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