324 CLINICAL REPORT
ActaDV ActaDV Advances in dermatology and venereology Acta Dermato-Venereologica
Substance P Antagonist Aprepitant Shows no Additive Effect Compared with Standardized Topical Treatment Alone in Patients with Atopic Dermatitis
Louise LÖNNDAHL 1, Mikael HOLST 2, Maria BRADLEY 1, Hassan KILLASLI 3, Johan HEILBORN 4, Martin A. HALL 5, Elvar THEODORSSON 6, Jadwiga HOLMBERG 7 and Klas NORDLIND 1
1
Dermatology and Venereology Unit, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, 2 Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institutet, Astrid Lindgren Children’ s Hospital, 3 Dermatology and Venereology Unit, Department of Medicine Huddinge, Karolinska Institutet and Karolinska University Hospital, 4 Dermatology Clinic, Hudcentrum, Hagastaden, 5 Dermatology Clinic, Stadions Läkarmottagning, Stockholm, 6 Department of Clinical Chemistry, Department of Clinical and Experimental Medicine, Linköping University, Linköping, and 7 Swedish Psoriasis Association Enskede, Stockholm, Sweden
Atopic dermatitis( AD) is a chronic, itchy, inflammatory skin disorder that may worsen due to stress and anxiety. Tachykinins have been suggested to be involved in the inflammation in AD, as well as pruritus. Aprepitant is a NK-1 receptor antagonist. This open randomized trial evaluated the effect of aprepitant added to topical treatment in adult patients with moderate – severe AD. The treatment group( n = 19) received 80 mg / day aprepitant for 7 days as a supplement to standardized topical treatment with a moderately strong steroid and a moisturizer. The control group( n = 20) received topical treatment alone. Patients were monitored for the extent of the disease( using SCORing of Atopic Dermatitis; SCORAD), pruritus, and scratching movements. In both the aprepitant-treated and the control groups there was a decrease in SCORAD, pruritus and scratching movements. How ever, there was no significant additional improvement in any of these parameters in the aprepitant-treated group compared with the control group.
Key words: anxiety; atopic dermatitis; aprepitant; depression; neurokinin 1 receptor; pruritus; SCORAD; substance P.
Accepted Nov 24, 2017; Epub ahead of print Nov 28, 2017 Acta Derm Venereol 2018; 98: 324 – 328.
Corr: Louise Lönndahl, Dermatology and Venereology Unit, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, SE 171 76 Stockholm, Sweden. E-mail: louise. lonndahl @ ki. se
Atopic dermatitis( AD) is a common, highly pruritic skin disease. For the majority of patients the symptoms decline after childhood, but, for some, AD continues into adulthood. AD per se is often associated with significant suffering for the patients as well as their families( 1). The disease often has a remitting / flaring course, which may be exacerbated by social, environmental and biological triggers, such as psychological and physical stress( 2).
The currently available standard treatment for AD is the use of moisturizers and topical steroids. If this treatment is not sufficiently effective, ultraviolet light( UV) and immunomodulator( e. g. cyclosporine, azathioprine, methotrexate) treatments are sometimes used. However, despite their higher potency, these treatments are not always effective. In addition, they carry the risk of severe side-effects, e. g. skin cancer, in the case of UV therapy, and infections and cancer in the case of immunomodulators.
As mentioned above, pruritus is a significant symptom of AD. Studies investigating the mechanisms of pruritus in humans( 3) and mice( 4) have reported substance P to be an important mediator of this symptom. Furthermore, substance P has been shown to induce wheal, flare and itching, when injected into human skin( 3). This is thought to be partly due to the release of histamine from mast cells. Substance P is also considered a proinflammatory neuropeptide, and alterations in the number of substance P positive nerve fibres and levels of substance P have been reported in lesional compared with control skin of patients with AD( 5).
The main receptor( R) of substance P is neurokinin( NK)-1R. A study in mice has suggested that a NK-1R antagonist( BIIF 1149 CL) could be effective in inhibiting scratching behaviour in mice( 6). In humans, promising results have been shown for a NK-1R antagonist, aprepitant( Emend R, Merck Sharp & Dohme( Sweden) AB, Stockholm, Sweden)( which is registered in Sweden for the treatment of nausea during chemotherapy in cancer patients), when treating different pruritic skin disorders, including prurigo and atopic diathesis( 7), and another report has shown a decrease in pruritus in patients with malignancies( metastatic solid tumours) and pruritus associated with their treatment( 8).
The present study evaluated the effect of addition of aprepitant in the short-term treatment of adult patients with moderate-severe AD, in an open randomized trial, compared with topical treatment with a steroid and moisturizer alone. The primary outcome was treatment effect and the primary endpoint was the extent of the disease( measured using SCORing of Atopic Dermatitis; SCORAD), while the secondary outcome was pruritus. In addition, psychodemographic parameters, measured with an anxiety and depression score, were investigated.
We hypothesized that treatment with aprepitant might decrease pruritus and scratching in patients with AD, even over a short period of treatment. Aprepitant could then be a possible candidate for use in an alternative doi: 10.2340 / 00015555-2852 Acta Derm Venereol 2018; 98: 324 – 328
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2018 Acta Dermato-Venereologica.