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 .