Risankizumab for the treatment of moderate‐to‐severe psoriasis: A multicenter, retrospective, 1 year real‐life study

Abstract Several new biologic agents targeting IL23/Th17 axis, such as risankizumab, have been developed for the treatment of psoriasis. The aim of the present study was to analyze the efficacy and safety of risankizumab in patients with moderate‐to‐severe psoriasis over a 52‐week period. A multicentric retrospective study was conducted in patients who initiated risankizumab between July 2019 and December 2020. Psoriasis Area and Severity Index—PASI was measured at baseline and after 4, 16, 28 and 52 weeks. Clinical responses were evaluated by PASI75, PASI90 and PASI100 at the same timepoints. Potential safety issues and adverse events (AEs) were collected. Univariable and multivariable logistic regressions were performed for variables predicting clinical response. One hundred and twelve patients with psoriasis were included. PASI90 response was achieved by 17.86% of patients at week 4, 72.22% at week 16, 91.0% at week 28 and 95.24% at week 52 (as observed analysis). No associations between the considered variables and the efficacy endpoints were retrieved, influence of variables such as Body Mass Index (BMI), baseline PASI or previous biologics were not shown. No serious safety issues or discontinuations related to adverse events were reported. Risankizumab showed high efficacy and a favorable safety profile, regardless of patient‐ and disease‐related factors.


| INTRODUCTION
Although psoriasis was originally regarded as primarily driven by Th1 cell-derived cytokines, the current accepted pathogenetic mechanism highlights the central role of IL23/Th17 axis in psoriasis pathogenesis. IL17 and IL23 are now considered as key mediators in psoriasis inflammatory cascade. 1,2 In fact, the production of IL23 by dermal dendritic cells (DCs) drives IL17 expression, leading to inflammation, neutrophilic chemotaxis and uncontrolled keratinocytes proliferation. 3 Based on these findings, several new biologic agents targeting IL23/Th17 axis have been developed for the treatment of plaque psoriasis. 4 These new drugs include risankizumab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody that selectively binds with high affinity to the p19 subunit of IL23. The efficacy and safety of risankizumab has been assessed in several phase III trials, 5 in which risankizumab showed superior efficacy to both placebo and ustekinumab, with a favorable safety profile. In ULTIMMA-1, at week 16, 75.3% of patients treated with risankizumab achieved a PASI90 response compared with 42% of patient receiving ustekinumab, similarly to the results obtained in ULTIMMA-2 study.
The efficacy and safety of risankizumab has been also assessed with "head-to-head" comparisons with other biologics, such as secukinumab in the IMMerge trial, 6 showing superior efficacy and similar safety compared with secukinumab, plus a more favorable dosing regimen.
Despite randomized controlled trials (RCTs) are essential to assess the efficacy and safety of a certain drug, real-life data often show differences between registration studies and clinical daily practice, since the latter displays a greater variability in demographical and clinical characteristics of treated patients in terms of age, disease severity, previous therapies and comorbidities. Thus, to integrate data from clinical trials with those of daily practice is essential to optimize patient's therapeutic management in a real-world setting. To our knowledge, few real-life studies have been performed to investigate the efficacy and safety of risankizumab, with an observation period ranging from 16 to 52 weeks. [7][8][9][10] The aim of this multicenter, retrospective study was to analyze the efficacy and safety of risankizumab in a population of patient from Lazio region in Italy affected by moderate-to-severe psoriasis, over a 52-week treatment period.

| MATERIALS AND METHODS
A retrospective analysis was performed in a cohort of patients with chronic plaque psoriasis, with or without psoriatic arthritis, who initiated treatment with risankizumab between July 2019 and December genital, facial areas) were collected at the time of initiation of biological therapy. In particular, data regarding the last biological treatment before starting risankizumab were collected, as well as the duration of the treatment and reasons of drug withdrawal. The severity of psoriasis was estimated by Psoriasis Area and Severity Index -PASI 11 measured at baseline and after 4, 16, 28 and 52 weeks, respectively. Data about potential safety issues and adverse events (AEs) were collected, including mild and serious adverse events. The entire study was conducted according to the principles of the Helsinki Declaration.

| Statistical analysis
Descriptive data were summarized using absolute and relative (%) frequencies for categorical variables, and medians and interquartile ranges (IR) for continuous non normally distributed variables. The percentual difference between the baseline PASI and the PASI score at different timing (4, 16, 28 and 52 weeks after the start of the treatment) was calculated to evaluate clinical responses set as PASI75, PASI90 and PASI100 (i.e., whether patients reached an improvement of 75%, 90% and 100% from baseline at weeks 4, 16, 28 and 52).
Univariable and multivariable logistic regressions were used to understand variables that predicted the clinical response. In addition, we also used the "non-responder imputation" analysis: conservative method that imputes that participants dropouts are considered nonresponders, regardless of actual response at the time of follow up loss. 12 Statistical significance was set at p-value <0.05. Analyses were performed by using STATA 13.0 Software (StataCorp, Texas).

| RESULTS
We analyzed data regarding 112 patients with moderate-to-severe psoriasis that started biological therapy with risankizumab. The median age was 48 years (range 39-57) and 71 (63.39%) were males.
More details regarding the demographic and clinical characteristics of the study population are described in Table 1.    promoting the pathogenetic role of tissue-resident memory cells. 29 In a study comparing changes in the immunologic profile during therapy with guselkumab and secukinumab, the former was proven to reduce the number of tissue-resident memory cells in favor of regulatory T cells, while, in the secukinumab group, a decrease in regulatory T cells was found. 30 The limitations of this study are mainly represented by the retrospective method of data collection and the absence of a control group. Moreover, the relatively small sample size and the smaller proportion of subjects reaching 52 weeks of treatment respect to the entire study population could result in a less accurate analysis of longterm effectiveness.
In Open access funding enabled and organized by Projekt DEAL.