Effectiveness, survival and safety of guselkumab attending to basal characteristics in moderate-to-severe psoriatic patients: a cohort study [version 2; peer review: 2 approved]

Background: Psoriasis is a chronic inflammatory disease which can impact quality of life. In the past decade multiple biologic treatments have been released with encouraging results. Guselkumab is a monoclonal antibody targeting IL-23p19. Multiple randomized clinical trials have demonstrated its efficacy in psoriasis, but response differences among patient subpopulations have not been extensively reported. Furthermore, patients in real life are often non-eligible for clinical trials and their responses may differ from pivotal studies. Methods: This is a retrospective, observational study of real clinical practice of patients receiving guselkumab treatment in Spain. Patients treated with guselkumab were included between February 2019 to December 2021. This study evaluates the potential differential effect of baseline demographic and disease characteristics on therapeutic responses to guselkumab. We measured effectiveness and survival by the psoriasis area and severity index, the dermatology life quality index as well as Kaplan meier curves, respectively. Categorical and quantitative variables are reported with frequencies, and with mean and standard deviation, respectively. Differences between groups in psoriasis area and severity index and dermatology life quality index, were calculated using a mixed-effects analysis. Survival was calculated using Kaplan meier curves and log-rank tests. Results: A total of 87 patients were included. In this study, our objective was to evaluate the effectiveness, safety and survival of guselkumab attending to demographic characteristics. No differences in psoriasis area and severity index or dermatology life quality index baseline values or therapeutic responses were noted at 52 weeks of follow-up among all the subgroups analysed (age, sex, psoriasis duration, body mass index, and comorbidities). A difference in drug survival was only seen between gender groups. Conclusions: Our research has demonstrated the consistency of guselkumab effectiveness across patient subgroups. No baseline features affected the effectiveness or drug survival of guselkumab, except for lower drug survival in female patients

Tildrakizumab: Efficacy, Safety and Survival in Mid-Term (52 Weeks) in Three Tertiary Hospitals in Andalucia (Spain)

Tildrakizumab (TIL) binds selectively to the p19 subunit of interleukin 23. Its introduction has managed to increase the levels of efficacy, safety (improving that previously presented by the anti-IL-12/23 class) and survival. Retrospective analysis of a multicenter, observational study of real clinical practice including patients with moderate-to-severe plaque psoriasis in treatment with TIL. This cross-sectional analysis includes information of patients between February 2019 to February 2022. A total of three tertiary hospitals in Andalusia (Spain) participated in this study. Analyses were performed “as observed” using IBM SPSS v28 for Windows. A total of 61 patients were included in the analysis. The mean age of our patients was 49.5 years; 50.18% of the patients were female and 34.42% of the patients had a BMI greater than 30. It was notable that 44.26% of our patients had scalp involvement. Almost 35% of the patients had psoriatic arthropathy, although skin involvement was predominant. At week 52 (n = 34), 68% of the patients presented an absolute PASI equal to or less than 1. Regarding the drug survival, eight patients discontinued treatment due to inefficacy: five primary and three secondary failures, and one death due to causes not drug related showing survival of 86% at week 52. In the analysis of subgroups of patients, we found that scalp involvement determined greater survival (94%), as well as a shorter duration of the disease (91.7% vs. 84.4% in those with less than 10 years versus more than 15 years of evolution) and with a lower number of previous biological therapies (100% naïve, 90% in those who have used one line of biological therapy and 82.1% in those who have completed two or more lines of biological treatment. Tildrakizumab showed excellent results in the control of psoriasis in the mid-term with an elevated number of patients maintaining treatment after 52 weeks. There were no statistically significant differences in the efficiency, safety or survival results of TIL between patients coming from previous therapies

Risankizumab: Efficacy, Safety, and Survival in the Mid-Term (52 Weeks) in Real Clinical Practice in Andalusia, Spain, According to the Therapeutic Goals of the Spanish Psoriatic Guidelines

Introduction. Risankizumab is a humanized monoclonal antibody of the immunoglobulin G1 (IgG1) type that binds selectively, and with high affinity, to the p19 subunit of interleukin-23 (IL-23), resulting in the inhibition of inflammation and clinical symptoms associated with psoriasis. Its introduction has managed to increase the levels of efficacy and safety (improving upon those previously presented by the anti-IL-23 class). Material and methods. Retrospective analysis of a multicenter, observational study of real clinical practice, including patients with moderate-to-severe plaque psoriasis in treatment with risankizumab. This cross-sectional analysis includes information on patients from May 2020 to June 2022. A total of six tertiary hospitals in Andalusia (Spain) participated in this study. Analyses were performed “as observed” using GraphPad Prism version 8.3.0 for Windows. Results. Regarding the percentage of patients who reached PASI 90 or PASI 100 at week 52, 92.5% achieved the therapeutic goal of PASI 90, and 78.5% reached PASI 100. When analyzing the results by absolute PASI, we found that 78.5% (n = 33) obtained PASI 0, 85.7% (n = 36) obtained PASI ≤ 1, and all patients achieved PASI ≤ 3 (disease control). Discussion. Risankizumab has shown promising results in the control of psoriasis in the long-term, with a high percentage of patients (>80%) maintaining PASI 90 and PASI 100 up to 52 weeks of treatment. No abnormal safety findings have been reported, and risankizumab appears to be a solid treatment in the different scenarios analyzed

Guselkumab as a switching strategy after anti-TNFα, anti-IL17, or anti-IL12/23 therapies in moderate-to-severe psoriasis.

The IL23/Th17 axis plays a strategic role in psoriasis (PSO). Guselkumab (GUS) is a selective inhibitor of the IL23p19 subunit. Its introduction has managed to increase the levels of efficacy, safety and survival in PSO. In real clinical practice, patients can loss effectiveness or suffered adverse events that forces a change in their treatments. There is scarce evidence of the effectiveness, safety, and survival of GUS in real clinical practice after anti-TNFα, anti-IL17, and/or anti-IL12/23. This is multicenter, observational and retrospective study of real clinical practice includes patients with moderate-to-severe plaque PSO in treatment with GUS. The objective of the study was to evaluate the effectiveness of GUS after anti-TNFα, anti-IL17, and anti-IL12/23. The study includes clinical information from February 2019 to February 2022. PASI, BSA, Pruritus, DLQI, survival, and safety were evaluated up to 76 weeks. Analyses were performed "as observed" using GraphPad Prism version 8.3.0 for Windows. A total of 103 patients were included in the analysis. At baseline there were significant differences between the anti-TNF, anti-IL17, and anti-IL12/23 groups for (1) dyslipidemia; (2) number of previous biological treatments and (3) PASI, BSA, VAS Pruritus, and DLQI scores. The effectiveness of GUS in terms of PASI, BSA, Pruritus, and DLQI was not impacted by previous biological alternatives. Treatment survival including discontinuations due to lack of effectiveness or safety reasons was 100%, 92.7%, and 92.1% for anti-TNFα, anti-IL17, and anti-IL12/23, respectively, at 130 weeks. No differences were found between groups. One adverse event was reported in the anti-LI12/23 group. The mid-term effectiveness, safety and survival of GUS if not impacted by previous biological therapy as anti-TNFα, anti-IL17, and/or anti-IL12/23. Our results indicate that GUS could be a switching strategy in patients who fail or present AE to other biological alternatives in moderate-to-severe PSO

Super-Responders in Moderate-Severe Psoriasis under Guselkumab Treatment: Myths, Realities and Future Perspectives.

A fast skin clearance is the main goal to achieve in psoriasis treatment. Patients that present a fast and exceptional improvement with treatment are called super-responders (SR). There is no consensus on the definition of SR with respect to psoriasis. Included herein is a retrospective analysis of a multicenter, observational study of real clinical practices including patients with moderate-to-severe plaque PSO undergoing treatment with Guselkumab (GUS). This cross-sectional analysis includes information on patients between February 2019 to February 2022. A SR is a patient that achieved a PASI = 0 at weeks 12 and 24. Analyses have been performed "as observed" using GraphPad Prism version 8.3.0 for Windows (GraphPad Software, San Diego, CA, USA, At baseline, the PASI is significantly correlated with VAS_pruritus, BSA, and DLQI, while DLQI is significantly correlated with VAS_pruritus. Significant correlations increase in number and magnitude over the follow-up time. In relation to the univariate logistic models carried out, only three variables showed a significant association with the super-responder variable: depression, VAS_pruritus, and DLQI.SR patients, who show a faster evolution in PASI and BSA improvement than non-SRs. Based on the results obtained, it would be possible to also include DLQI and VAS_pruritus in the broader concept of the SR

Guselkumab dosing interval optimization in adult patients with moderate-to-severe psoriasis switching from ustekinumab.

Psoriasis (PSO) is an inflammatory disease that emerges as a dysregulation of the interleukin 23 (IL23)/Th17 axis. There are many biologic alternatives to treat PSO that are administered monthly, every 2 months and every 3 months. Guselkumab (GUS) is a fully human monoclonal antibody, that selectively blocks IL-23 through binding to its p19 subunit. There is scarce evidence on dose optimization of GUS in psoriatic patients. Retrospective, observational case series review which includes patients with moderate-to-severe PSO who switched from ustekinumab to GUS as standard dosing or every 12 weeks, regarding daily clinical practice of every dermatology unit. Clinical and demographic data from patients were included from February 2019 to October 2021. Analyses were performed "as observed" using GraphPad Prism version 8.3.0 for Windows (GraphPad Software, San Diego, CA, USA, www.graphpad.com). A total of 30 patients were included in this study: 20 receiving GUS as standard of care (SC) and 10 receiving an optimized dosing (Q12W) (GUS every 12 weeks without induction). The Q12W group presented greater percentage of comorbidities and was less refractory to previous biologic treatments. After receiving GUS as SC or Q12W, psoriasis area severity index and dermatology life quality index improved dramatically in both groups up to 52 weeks. Survival was 87.2% and 100% for the SC and Q12W, respectively, and there were not safety signals. Our case series of 10 patients receiving GUS every 12 weeks without induction showed a good effectiveness and safety profile accompanied by an excellent treatment survival. However, more studies are needed to provide strong evidence of dosing alternatives different than SC

Bimekizumab: Short-Term Effectiveness and Safety in Real Clinical Practice in Andalucia, Spain

Introduction: Psoriasis, a chronic inflammatory skin disease, affects 2–10% of the population globally. Bimekizumab (BMK), a monoclonal antibody targeting IL-17, is a dual inhibitor of IL17 A and F that has shown efficacy in treating moderate to severe plaque psoriasis. This real-world evidence (RWE) study aims to assess BMK’s efficiency and safety in naïve and refractory patients. Material and methods: A retrospective analysis of a multicenter observational study included 22 patients treated with BMK from April 2023 to February 2023 in five Andalusian hospitals. Ethical approval was obtained, and patients provided informed consent. Assessment criteria encompassed Psoriasis Area and Severity Index (PASI), body surface area (BSA), VAS pruritus, Dermatology Life Quality Index (DLQI), and minimum disease activity (MDA) at 0, 4, 12, and 24 weeks. Results: Patients, predominantly with plaque psoriasis, exhibited significant improvements in PASI (baseline 15.7 to 0.4 at week 16), BSA (baseline 20.7 to 0.43 at week 16), DLQI (baseline 17.93 to 0.43 at week 16), and pruritus (baseline 7.12 to 0.4 at week 16). At week 16, 95.4% achieved MDA. No safety concerns or treatment discontinuations were reported. Discussion: This RWE study aligns with pivotal clinical trials, confirming BMK’s efficacy and safety. Notably, BMK demonstrated rapid and sustained psoriasis clearance, even in challenging areas. The study’s limitations include a small sample size, suggesting the need for further exploration of patient-reported outcomes. Conclusion: Bimekizumab exhibited optimal efficacy and safety profiles in treating moderate to severe plaque psoriasis in a real-world setting. Rapid response, sustained clearance, and favorable safety outcomes contribute to improved patient experiences. Future research could delve into patient-reported outcomes and expand sample sizes to enhance the understanding of BMK’s real-world effectiveness