Two studies presented at the annual meeting of the American Academy of Dermatology in San Francisco were devoted to acne therapy. Both tested a fixed combination of adapalene and benzoyl peroxide – once with certain modifications regarding the amount of active ingredient, the other time over a period of nine months. In addition, atopic dermatitis was the focus of interest.
The chronic inflammatory disease acne affects approximately 85% of people between the ages of twelve and 24 and can involve serious psychological and physical sequelae. Although most studies are designed for a twelve-week treatment, a long-term approach is essential. The success of therapy is critically dependent on how well the patient accepts and follows the therapy. Parameters such as quality of life and adherence should therefore be considered in any case when choosing medication. Therapeutically, drug combinations are most useful because they target the pathogenetic factors of acne via different mechanisms of action.
Combination of adapalene and benzoyl peroxide
For some time now, the fixed combination of adapalene 0.1% and benzoyl peroxide 2.5% has been available as a gel (Epiduo®), the efficacy and safety of which have been demonstrated in the treatment of acne. A new topical gel has now been developed containing adapalene at a concentration of 0.3% combined with benzoyl peroxide (A/BPO) in the above-mentioned active ingredient amount.
A randomized, controlled multicenter study presented at the AAD Congress tested the success of this gel in acne therapy. 503 individuals aged at least 12 years (mean 19.6) with moderate to severe acne vulgaris and facial involvement (≥20 inflammatory, ≥30 noninflammatory lesions) participated in the study. They applied the following agents once daily for twelve weeks:
- Group 1: 0.3% A/BPO, n=217
- Group 2: 0.1% A/BPO, n=217
- Group 3: ineffective vehicle, n=69.
The questions to be answered were: How many patients achieve a treatment success, defined as an improvement on the IGA scale (“investigator global assessment”) of at least two degrees? And to what extent does the lesion number change? The study was not designed to compare the two A/BPO combinations.
The 0.3% gel was significantly superior to vehicle (treatment success 33.7 vs. 11.0%). The absolute changes in the number of inflammatory (-27 vs. -14.4) and noninflammatory lesions (-40.1 vs. -18.4) were also significant-analogous to the relative changes (-68.7 vs. -39.2% and -68.3 vs. -37.3%, respectively). After one week of treatment, the difference in the number of inflammatory lesions had already reached statistical significance; a significant superiority was found for the therapeutic success from week 8 onwards. A subgroup with severe acne (IGA = 4) showed comparable, and in the majority even better, results in all three points.
Safety is good
The 0.3% combination was tolerated locally equally well as the 0.1% gel. Treatment-associated adverse events were mild to moderate. Only one person in each of the two verum groups terminated treatment prematurely – in the case of the 0.3% gel, a recurrence of atopic dermatitis was responsible. In view of the results, it would now be interesting to set up a study with sufficient power to compare the two concentrations. Precisely because the 0.3% gel tended to be superior to the 0.1% formulation in the present study.
And what about long-term treatment?
Also presented at the congress was a large observational study over nine months, this time again with the baseline drug dose consisting of adapalene 0.1% and benzoyl peroxide 2.5%. The study confirmed the long-term effect under everyday practical conditions.
86% of participants had moderate acne at baseline. On average, they were 14 years old and the majority were male. Thirty-seven patients had received acne treatment, mostly with topical antibiotics, three months before the study. During the study, the majority were treated with the gel alone, but 21% applied additional systemic or topical therapy. Unfortunately, this group was not evaluated separately.
- 5131 subjects were evaluated for efficacy. Mean acne severity improved significantly from 5.6 (baseline) to 1.9 (after nine months) according to the revised Leeds Scale. In 26%, the acne had completely disappeared at the end of the study, i.e. was no longer visible. Quality of life improved significantly during the course of treatment. Adherence was a good 84% at nine months. According to study authors, this is a crucial factor to consider in drug selection for long-term treatments.
- 5141 people were evaluated with regard to safety. According to medical assessment, tolerance was good to very good in 90% of patients. Dryness (31%), erythema (24%), and scaling (22%) were most common. Only just 1.7% of participants discontinued therapy because of this. The vast majority of skin irritations were mild and subsided as soon as the gel was discontinued.
Atopic dermatitis and lymphoma risk
In a systematic review also presented at the congress, Laureline Legendre, MD, of the University of Toulouse, examined the risk for lymphoma in patients with atopic dermatitis. It is unclear and controversial whether this population is actually at increased risk for lymphoma. The type of therapy was included in the study because, finally, the potential influence of topical calcineurin inhibitors on the development of lymphoma has received much attention in recent years. Of the 3979 articles retrieved from the Pubmed, Cochrane, and Scopus data platforms, the authors considered 24 studies to be methodologically and substantively adequate after close review.
- The risk of lymphoma was slightly but significantly increased across all cohort studies (RR 1.43; 95% CI 1.12-1.81). In contrast, no significant increase was found in case-control studies (OR 1.18; 95% CI 0.94-1.47).
- Across all studies, neither pimecrolimus nor tacrolimus exerted a significant effect on lymphoma risk.
- Three studies showed an increase in risk associated with severe forms of atopic dermatitis. Consequently, at first glance, disease severity appears to be a relevant risk factor.
- Under highly potent topical corticosteroids, the odds of developing lymphoma were significantly increased by 73% in case-control studies (OR 1.73; 95% CI 1.52-1.97).
The authors point out weighty limitations regarding the diagnosis of atopic dermatitis and lymphoma classification. For example, misinterpretation of cutaneous T-cell lymphoma as severe atopic dermatitis may be partly responsible for the associations. If T-cell lymphoma was misdiagnosed as severe atopic dermatitis and high-potency topical corticosteroids were used, this may have caused a spurious association.
Systemic therapies for severe atopic dermatitis in childhood.
Atopic dermatitis mainly affects children and has become increasingly common in recent decades: The lifetime prevalence of children born after 1980 is 15-20%. Effective control can be achieved with approved topical medications in a majority of pediatric patients. However, severe disease states require systemic treatment.
Unfortunately, the evidence-based data on such therapies in the pediatric population is limited. Due to a lack of studies, there are also no well-established treatment standards (e.g., on dosage, duration of therapy, or differences in effectiveness between agents). On the FDA side, no systemic drug is approved for severe pediatric atopic dermatitis, according to the presenters, and access to off-label use of agents is often denied in children. The severe forms in particular are associated with an extraordinarily high morbidity: Both physically and emotionally, and in terms of quality of life, the condition causes great stress (e.g., it causes sleep disturbances) [1].
Therefore, the aim of a small, prospective, multicenter study was to assess the efficacy and safety of the four most commonly used immunosuppressants (methotrexate, ciclosporin, azathioprine, mycophenolate) for moderate to severe forms of atopic dermatitis. All four agents have been used in children, and all four have some evidence, albeit varying in strength, in atopic dermatitis [2,3].
22 Patients aged 1-20 years were included (mean age at entry was 8.45 years). According to the IGA scale, 41% suffered from severe (grade 4) and 55% from very severe atopic dermatitis (grade 5). Treatment success was defined as a decrease of at least three points in IGA or an IGA score of ≤2. 73% of patients achieved this status after an average of 5.7 months. In six patients, therapy failed or was discontinued. Lack of adherence, the conscious decision of the parents and, in one case, severe side effects were reasons for this. The following values were obtained for the individual active ingredients:
- In the methotrexate group, 70% achieved treatment success after an average of 5.1 months.
- Azathioprine resulted in treatment success in 71% after an average of 6.4 months.
- With ciclosporin, 67% reached goal after an average of 3.4 months.
- With mycophenolate, the rate was 100% after an average of 8.5 months.
Only two patients had to change treatment due to severe side effects. Since the data must be considered preliminary, do not show significance, and the study size is severely limiting, the validity of the study must be taken with caution. Nevertheless, the authors conclude that the four agents appear to be similarly effective and safe in the treatment of pediatric atopic dermatitis – at least no clear differences were shown and no agent was clearly superior to the others.
Source: American Academy of Dermatology (AAD) 73rd Annual Meeting, March 20-24, 2015, San Francisco.
Literature:
- Camfferman D, et al: Eczema and sleep and its relationship to daytime functioning in children. Sleep Medicine Reviews 2010; 14: 359-369.
- Sidbury R, et al: Guidelines of care for the management of atopic dermatitis. J Am Acad Dermatol 2014; http://dx.doi.org/10.1016/j.jaad.2014.03.030.
- Roekevisch E, et al: Efficacy and safety of systemic treatments for moderate-to severe atopic dermatitis: A systematic review. J Allergy Clin Immunol 2014; 133(2): 429-438.
DERMATOLOGY PRACTICE 2015; 25(3): 32-34
