Real world practice indirect comparison between guselkumab and risankizumab: Results from an Italian retrospective study

Abstract IL‐23‐inhibitors, such as guselkumab and risankizumab, represent the newest class of biologics approved for psoriasis. Phase III trials have shown their efficacy and safety. However, real life data are still scant. to indirectly compare the effectiveness, safety and tolerability of guselkumab and risankizumab in real world practice. An Italian single‐center retrospective cohort study enrolling moderate‐to‐severe psoriasis patients from September 1, 2018 and December 31, 2020 was performed to indirectly compare guselkumab and risankizumab efficacy and safety. Sixty eight patients were included (36 received guselkumab and 32 risankizumab). The groups were comparable for all analyzed characteristics, except for mean psoriasis duration (p < 0.01) which was higher for guselkumab. In guselkumab group, mean PASI reduced from 16.1 ± 6.4 (baseline) 2.1 ± 0.9 (week‐28) (p < 0.001) up to 0.9 ± 0.8 (week‐44) (p < 0.001). In risankizumab group mean PASI decreased from 13.5 ± 4.9 (baseline) 1.9 ± 0.8 (p < 0.001), (week‐28) (p < 0.001) up to 0.9 ± 0.4 (week‐40) (p < 0.001). No significant difference in mean PASI and BSA were observed between the treatments. No cases of serious AEs, injection site reaction, candida, malignancy, cardiovascular events were reported in both groups. Guselkumab and risankizumab showed favorable efficacy and safety profile, being comparable in terms of PASI90 and PASI100 responses as well as in AEs frequency and discontinuation rates.


| INTRODUCTION
Psoriasis is a chronic inflammatory skin disease that may be associated with numerous comorbidities, resulting in a considerable impact on patients' quality of life. 1 Psoriasis pathogenesis is complex with a unique trigger or aetiologic factor being not detected. Recent major research advantages lead to the development of biologic therapies targeting specific cytokines engaged in the chronic inflammation which sustain psoriasis. 2 These therapies include drugs targeting Tumor Necrosis Factor (TNF)-α, Interleukin (IL)-17, and IL-12/23. The newest class of biologics include drugs selectively targeting IL-23 such as risankizumab and guselkumab which have been recently approved for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. [3][4][5] Guselkumab and risankizumab are human monoclonal-antibodies that specifically inhibit intracellular and downstream signaling of IL-23 by binding to its p19 subunit. 3,6,7 Guselkumab was the first anti IL-23 agent being available on the market for the treatment of moderate-to-severe psoriasis. 3 Its efficacy and safety have been showed by VOYAGE-1 and VOYAGE-2, two phase-III multicenter, randomized, double-blind, placebo and comparator-controlled clinical trials. 8,9 Moreover, recently real-life studies confirmed trials results, showing guselkumab as a safe and effective treatment. 3,[10][11][12][13][14][15][16] Risankizumab is another anti-IL23 approved in both USA and Europe. 17 Two phase-III trials, UltIMMa-1 and UltIMMa-2, have reported a higher efficacy of risankizumab respect to ustekinumab 17 whereas the phase-III trial IMMvent showed its superiority against adalimumab. 18 Both guselkumab and risankizumab efficacy and safety have been compared with anti-TNF (adalimumab), anti-IL-12/23 (ustekinumab) and anti-IL-17 (secukinumab), showing promising results in PASI90 and PASI100 responses. 8,9,18,19 However, to date, study comparing guselkumab and risankizumab safety and efficacy in real world practice are still lacking. Real life studies are needed in order to verify the efficacy and safety of recently approved biologics for psoriasis in a more complicated setting of patients which are usually excluded from clinical trials. Herein, we performed a retrospective cohort study using real-world data to indirectly compare the efficacy and safety of guselkumab and risankizumab in psoriasis patients.

| METHODS
An Italian single-center retrospective cohort study enrolling moderate-to-severe patients attending the Psoriasis Care Center of the University of Naples Federico II, Naples, Italy from 1 À September-2018 and 31-December-2020, was performed to indirectly compare guselkumab and risankizumab efficacy and safety. Inclusion criteria were: (i) moderate-to-severe plaque psoriasis diagnosed since at least 1 year; (ii) subjects starting guselkumab or risankizumab treatments and being treated for at least 12 weeks. Patients were treated with standard dose of guselkumab (100 mg sc administered by subcutaneous injection at Week 0 and Week 4, followed by a maintenance dose every 8 weeks) or with standard dose of risankizumab (two injections of 75 mg subcutaneously at Week 0, Week 4, and then every 12 weeks). At baseline, the following items were registered for each patient: (i) personal and demographic data; (ii) duration of psoriasis

| Statistical analysis
Continuous variables were displayed as mean ± SD, whereas categorical variables or as number and proportion of patients. Demographic and clinical characteristics of the sample were described through absolute and relative frequencies (%), means and/or SDs where appropriate. T-test and Chi-squared test were used to compare the quantitative and qualitative characteristics of the populations treated with the two different drugs. A p value of <0.05 was considered statistically significant. All statistical analyses were performed using GraphPad-Prism 4.0 (GraphPad Software Inc., La Jolla, CA, USA).
In risankizumab group they were represented by upper respiratory  12 On the other hand, to date fewer data about risankizumab real-life efficacy have been reported due to its more recent approval and availability. 27,28 In an Italian single center 16 weeks, retrospective study, efficacy and safety of risankizumab resulted comparable to trials results. Particularly, PASI-100 and PASI-90 were achieved by 49.1% and 63.2% respectively. 27 Moreover, in a previous single-centre, prospective study we assessed risankizumab efficacy and safety in patients who had previously failed anti-IL17, anti-IL12/23 or anti-IL23 inhibitor showing risankizumab as a promising therapeutic option in patients who failed these drugs. 17 In addition, in a recent study risankizumab efficacy had been evaluated in patients who also initially failed guselkumab. 29 32 Hence, a prophylactic treatment discontinuation in order to prevent infection risk or possible negative COVID-19 outcomes is not required. 32 In conclusion, our study revealed that in real world practice, guselkumab and risankizumab showed an elevated efficacy and safety profile, being comparable in terms of PASI90 and PASI100 responses as well as in AEs and discontinuation rates. However, more data are needed to confirm our results, with a larger study population for both groups, in order to evaluate the real impact and the exact role that both treatments may have in psoriasis management.

| LIMITATIONS
The relatively small sample size and the retrospective nature of the survey may limit the generalizability of our results.

AUTHOR CONTRIBUTIONS
All authors contributed equally in producing this work.

DATA AVAILABILITY STATEMENT
Data sharing is not applicable to this article as no new data were created or analyzed in this study.