Protocol Title Efficacy of a second Il-17 inhibitor in patients with psoriasis: a systematic review and meta-analysis

Authors Nikolai Dyrberg Loft1,2 MD Anne-Sofie Halling1,2 MD Alexander Egeberg1,2 MD, PhD Lone Skov1,,2 MD, PhD, DmSci

1Department of and Allergy, Herlev and Gentofte Hospital, University of , Hellerup, 2Copenhagen Research Group for Inflammatory Skin (CORGIS), Herlev and Gentofte Hospital, Hellerup, Denmark

Aim The aim of this systematic review and meta-analysis is to review the efficacy of IL-17 inhibitors in patients with psoriasis with previous treatment with an IL-17 inhibitor.

Study design A systematic review and meta-analysis

Eligibility criteria For studies to be included they must 1) include psoriasis patients undergoing treatment with IL-17 inhibitors and previous treated with another IL-17 inhibitor, 2) include at least 10 psoriasis patients, 3) present data on one of the following: proportion of psoriasis patients achieving 75, 90 or 100% reduction in Psoriasis Area and Severity Index (PASI-75, -90, and -100), or the proportion of patients achieving an Physician Global Assessment (PGA) of 0/1, and 4) be published in English.

Literature search Two independent authors (N.D.L. and A.H.) will search and screen 2 medical databases (Pubmed and Embase) using the search term: "(secukinumab or ixekizumab or brodalumab) and

psoriasis". No search filters will be applied. Furthermore, reference lists of key articles and relevant reviews will be screened. All articles will be screened from inception of the databases until March 2020.

Selection of studies and data extraction The literature search will be performed in accordance with PRISMA guidelines and full search 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: Author information, publication year, design, country. 2. Populations characteristics: Age and gender 3. IL-17 inhibitor: Current IL-17 treatment, dosage, and frequency. Previous IL-17 treatment and reason of discontinuation. 4. Efficacy of IL-17 inhibitor: the proportion of psoriasis patients achieving PASI-75, 90 and 100, and the proportion of patients achieving an PGA of 0/1.

Data synthesis Data synthesis will be conducted using StatsDirect version 3 (StatsDirect Ltd., Cheshire, UK). Proportion meta-analysis will be performed to obtain pooled prevalence. Heterogeneity of studies will be assessed with Cochran’s Q-test, using a significance level of 0.05, and I² statistic. Estimates will be conducted using random effects model (DerSimonian and Laird). Should studies present substantial heterogeneity, then additional sensitivity analyses will be performed. Publication bias will be assessed with funnel plots and Egger's test. The PRISMA guidelines will be followed when reporting results of this study.

Corresponding author Nikolai Dyrberg Loft Department of Dermatology and Allergy, Herlev and Gentofte Hospital, , 2900 Hellerup, Denmark Email: [email protected]

Language English

Country Denmark