Study protocol

Time to Onset of Action for Biological and Systemic Treatments for Adult

Title: Time to Onset of Action for Biological and Systemic Treatments for Adult Atopic Dermatitis

Authors Farnam B. Sedeh1,2, Anne-Sofie Halling-Overgaard 1,2, Lauge M. Brundvad1,2, Farzad Alinaghi1 Alexander Egeberg1,2 , Jacob P. Thyssen1-3 1 Department of and Allergy, Herlev and Gentofte Hospital, University of , Hellerup, . 2 Copenhagen Research Group for Inflammatory Skin (CORGIS), Hellerup, Denmark. 3 LEO Pharma Foundation Skin Research Centre.

Aim The aim of this systematic review is to examine the time of onset of action for systemic and biological treatments in atopic dermatitis (AD) patients. The primary outcome is the average time for, respectively 25% and 50% of AD patients to achieve Eczema Area and Severity Index (EASI)-50, EASI75, and EASI90. The secondary outcome is the average time for, respectively 25% and 50% of AD patients to achieve SCORing Atopic dermatitis (SCORAD)-50, SCORAD75 and SCORAD90.

Study Design A systematic review

Eligibility criteria Clinic trials and observational studies are included if they: 1) investigate treatment with biologics or systemic therapies in AD patients, 2) have data on the average time for 25% or 50% of AD patients to achieve EASI50, EASI75 or EASI90 or SCORAD50, SCORAD75 or SCORAD90, and 3) include at least 10 adult AD patients in each treatment group.

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Literature search Three independent authors (F.B.S., L.M.B.AH will search Pubmed and EMBASE using the following search terms: 1): (atopic dermatitis AND ( OR cyclosporine OR azathioprine OR mycophenolate OR OR OR OR nemolizumab OR baricitinib OR tofacitinib OR OR OR OR OR OR OR apremilast OR OR ZPL-3893787 OR PF-04965842 OR ANB-020 OR ALX-101 OR GBR-830)) OR omalizumab OR ustekinumab)) 2): (atopic dermatitis and prednisolone)

Selection of studies and data extraction The literature search will be performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and full research process and reasons for exclusion of studies, will be outlined in a PRISMA flow diagram. For all included publications we will retrieve data on: 1. Study details: Authors, publication year, study period, phase and name of clinical trial (if it is a clinical trial), and dose. 2. Populations characteristics: Age (mean), mean baseline EASI and SCORAD score, characteristics of control group, concurrent topical treatment allowed, total number of participants, prior treatments/washout, and AD severity for inclusion in studies. 3. Atopic dermatitis: outcome measurements including time until 25% and 50 % of AD patients retrieve EASI50, EASI75 and EASI90 as well as SCORAD50, SCORAD75 and SCORAD90.

Data synthesis StatsDirect software (Version 3, StatsDirect Ltd, Cheshire, UK) will be used to calculate the time to treatment response, presented at the mean (SD) weighted by study sample.

Corresponding author Jacob P. Thyssen, MD PhD DMSc

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Department of Dermatology and Allergy, Herlev and Gentofte Hospital, , 2900 Hellerup, Denmark. E-mail: [email protected]

Anticipated/actual start date 1th of July 2018 Language English Country Denmark

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