Combinations are hot in AD treatment

In her lecture, Dr Magdalena Trzeciak (Medical University of Gdansk, Poland) advocated combination therapy in AD [1]. Not only can topicals be combined, even novel targeted therapies work better with additional topical treatments. There are many good reasons for using combinations: they provide additive or synergistic efficacy compared to monotherapy, and as the required dose of individual agents can be reduced, combinations are often more tolerable compared with monotherapy.

Emollients are the cornerstone of AD treatment: they prolong time to flare, reduce the number of flares and the amount of topical corticosteroids (TCS) needed to achieve similar reductions in eczema severity [2]. Their use is also recommended in current guidelines for all AD patients [3]. Emollients restore the impaired barrier function of the epidermis, prevent microbes and irritants from entering the skin, reduce pruritus, and prevent water loss. Even petrolatum has shown not only to be an “inert” moisturiser, but to significantly upregulate antimicrobial peptides and innate immune markers, and improve epidermal differentiation [4]. Emollient use in newborns at high risk for AD even lowers the relative risk for developing AD by about 50% [5].

Moisturiser: the base of every AD therapy

Moisturisers combined with active treatment gave better results than active treatment alone [2]. “Therefore, emollients and any other therapy are the most important combination in AD treatment”, said Dr Trzeciak. Another useful combination is TCS and topical calcineurin inhibitors (TCI). “One should be aware of the fact that more than 40% of our patients have a TCS phobia,” emphasised Dr Trzeciak. Due to their efficacy, TCS are still the first-line treatment in the acute phase. TCIs are indicated in problem areas such as the face, intertriginous sites, or anogenital area. They have the advantage that their use does not lead to atrophy, glaucoma, or cataracts. However, side effects are burning and irritation of the skin, and UV protection should be recommended to all patients.

Several trials have shown that the (sequential) combination of TCS and TCIs is more effective than monotherapy. During flares, the sole use of TCS is recommended, whereas treatment with TCIs should be performed between flares. “Between flares, TCIs should be applied to previously affected areas of skin, whereas emollients are indicated on the entire body,” recommended Dr Trzeciak. A study on intermittent topical betamethasone butyrate propionate/tacrolimus sequential therapy showed that it improved lichenification and chronic papules of patients with AD more efficiently than the so-called proactive therapy, consisting of an intermittent topical betamethasone butyrate propionate/emollient sequential therapy after 4 weeks of treatment [6]. Another study showed that simultaneous application of a TCS and TCI is superior to monotherapy with TCI with regard to the scores for erythema, lichenification, pruritus, scaling/dryness, and oozing/crusting [7]. Interestingly, the combination was also better tolerated. Also, the short-term combination of (diluted) TCS and/or emollients and wet wrap therapy was shown to be effective in patients with severe AD (defined as result in the Severity Scoring of Atopic Dermatitis [SCORAD] of >50) [8].

Combinations are also possible with novel targeted therapies, e.g. the IL-4/IL-13 inhibitor dupilumab. This was shown in the LIBERTY AD CHRONOS trial [9]. In this trial, all patients were treated with TCS with or without TCIs, and additionally received dupilumab (every week or every 2 weeks). Dupilumab added to standard TCS therapy improved AD signs and symptoms with acceptable safety [9]. The efficacy of a combination therapy of TCS and targeted treatment was also shown in a phase 2b study in which a combination of TCS with the anti-IL-13 agent tralokinumab was associated with early and sustained improvement in AD symptoms compared with TCS and placebo [10].

1 Trzecicak M. 24th World Congress of Dermatology, 10-15 June 2019, Milan, Italy.

2 van Zuuren EJ, et al. Cochrane Database Syst Rev 2017:CD012119.

3 Wollenberg A, et al. J Eur Acad Dermatol Venereol 2018;32:657-82.

4 Czarnowicki, T et al. J Allergy Clin Immunol 2016;137:1091-1102.

5 Simpson EL, et al. J Allergy Clin Immunol 2014;134:818-23.

6 Nakahara T, et al. J Dermatol 2004;31:524-8.

7 Hebert AA, et al. Cutis 2006;78:357-63.

8 Oranje AP, et al. J Eur Acad Dermatol Venereol 2006;20:1277-86.

9 Blauvelt A, et al. Lancet 2017;389:2287-2303.

10 Wollenberg A, et al. J Allergy Clin Immunol 2019;143:135-141.

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