IL-23 inhibition for the treatment of psoriatic arthritis

Mohanakrishnan, Raagav; Beier, Secia; Deodhar, Atul

doi:10.1080/14712598.2021.1938538

Cited by 12 publications

(6 citation statements)

References 49 publications

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“…Guselkumab has recently received approval also for the treatment of psoriatic arthritis 26 . At week 16, patients with PsA were less likely to achieve a PASI75 and absolute PASI ≤ 2.…”

Section: Discussionmentioning

confidence: 99%

“…Guselkumab has recently received approval also for the treatment of psoriatic arthritis. 26 At week 16, patients with PsA were less likely to achieve a PASI75 and absolute PASI ≤ 2. However, after 1 year of treatment, patients with and without PsA achieved comparable responses, showing slower effectiveness of guselkumab in those with concomitant joint involvement.…”

Section: T a B L Ementioning

confidence: 92%

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Real‐life effectiveness and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: A 104‐week multicenter retrospective study – IL PSO (ITALIAN LANDSCAPE PSORIASIS)

Gargiulo

Ibba

Malagoli

et al. 2023

Acad Dermatol Venereol

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Background Guselkumab is a fully human monoclonal antibody that binds selectively to the p19 subunit of interleukin‐23, which has shown efficacy in patients with previous incomplete response to ustekinumab in the NAVIGATE clinical trial. [Correction added on [28‐02‐2023], after first online publication: ‘humanized monoclonal antibody’ has been changed to 'fully human monoclonal antibody' in the preceding sentence.] Objectives We conducted a 104‐week multicenter retrospective study to assess the effectiveness and safety of guselkumab in patients affected by plaque psoriasis with an inadequate response to ustekinumab in a real‐life setting. Methods Our retrospective study included 233 adults affected by moderate‐to‐severe plaque psoriasis, enrolled in 14 different Italian centres, and treated with guselkumab after failing therapy with ustekinumab. Patient characteristics and PASI (Psoriasis Area and Severity Index) score at each visit (baseline, weeks 16, 52 and 104) were recorded. The percentages of patients achieving 75%, 90% and 100% (PASI 75, PASI 90 and PASI 100) improvement in PASI, compared with baseline, were registered. Results At week 52, PASI 75 was reached by 89.88% of patients, PASI 90 by 71.43%, PASI 100 by 58.83% and absolute PASI ≤2 by 90.48%. At week 104, similar effectiveness results were observed. Compared to the NAVIGATE trial, we observed higher rates of PASI 75/90/100. Patients with the involvement of difficult‐to‐treat areas were significantly less likely to achieve PASI90 and PASI100 at week 16. Obese patients had significantly lower rates of PASI75 and PASI ≤2 at week 52. At week 104, comparable responses were observed among all patients' subgroups, regardless of BMI status, involvement of difficult‐to‐treat areas, presence of cardiometabolic comorbidities and concomitant psoriatic arthritis. No significant safety findings were reported throughout the study. Conclusion Our data suggest that the efficacy of guselkumab in patients with inadequate response to ustekinumab for plaque psoriasis in ‘real‐life’ clinical practice is comparable with NAVIGATE study with higher percentages of patients achieving PASI90 and PASI100 at weeks 16, 52 and 104.

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“…Guselkumab has recently received approval also for the treatment of psoriatic arthritis 26 . At week 16, patients with PsA were less likely to achieve a PASI75 and absolute PASI ≤ 2.…”

Section: Discussionmentioning

confidence: 99%

Section: T a B L Ementioning

confidence: 92%

Real‐life effectiveness and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: A 104‐week multicenter retrospective study – IL PSO (ITALIAN LANDSCAPE PSORIASIS)

Gargiulo

Ibba

Malagoli

et al. 2023

Acad Dermatol Venereol

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“…Similarly, IL-23, produced by MDSCs, has been linked to the emergence of the castration resistance status through the activation of AR pathway and could promote tumor progression by regulating the Th17 response and Treg functions [ 68 ], suggesting a role for its blockade in this clinical setting. Anti-IL-23 therapy, such as guselkumab, was recently approved by the FDA to treat psoriatic arthritis, and its effectiveness could also be explored in PCa [ 69 ].…”

Section: Future Perspectivesmentioning

confidence: 99%

Immune Checkpoint Inhibitors in Advanced Prostate Cancer: Current Data and Future Perspectives

Rebuzzi

Rescigno

Catalano

et al. 2022

Cancers

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In the last 10 years, many new therapeutic options have been approved in advanced prostate cancer (PCa) patients, granting a more prolonged survival in patients with metastatic disease, which, nevertheless, remains incurable. The emphasis on immune checkpoint inhibitors (ICIs) has led to many trials in this setting, with disappointing results until now. Therefore, we discuss the immunobiology of PCa, presenting ongoing trials and the available clinical data, to understand if immunotherapy could represent a valid option in this disease, and which subset of patients may be more likely to benefit. Current evidence suggests that the tumor microenvironment needs a qualitative rather than quantitative evaluation, along with the genomic determinants of prostate tumor cells. The prognostic or predictive value of immunotherapy biomarkers, such as PD-L1, TMB, or dMMR/MSI-high, needs further evaluation in PCa. Monotherapy with immune checkpoint inhibitors (ICIs) has been modestly effective. In contrast, combined strategies with other standard treatments (hormonal agents, chemotherapy, PARP inhibitors, radium-223, and TKIs) have shown some results. Immunotherapy should be better investigated in biomarker-selected patients, particularly with specific pathway aberrations (e.g., AR-V7 variant, HRD, CDK12 inactivated tumors, MSI-high tumors). Lastly, we present new possible targets in PCa that could potentially modulate the tumor microenvironment and improve antitumor activity with ICIs.

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“…Currently available bDMARDs include tumor necrosis factor (TNF) inhibitors, interleukin (IL)12/23 inhibitors, IL-17 inhibitors, and IL-23 inhibitors. Although IL-23 inhibitors are comparatively newer and further research is still in progress, some studies have confirmed their safety and efficacy [ 9 – 11 ].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of IL-23 inhibitors in the treatment of psoriatic arthritis: a meta-analysis based on randomized controlled trials

Huang

Shentu

et al. 2023

Immunol Res

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In recent years, the use of interleukin (IL) 23 inhibitors in the treatment of psoriatic arthritis (PsA) has been the subject of much research. By specifically binding to the p19 subunit of IL-23, IL-23 inhibitors block downstream signaling pathways and inhibit inflammatory responses. The objective of this study was to assess the clinical efficacy and safety of IL-23 inhibitors in the treatment of PsA. PubMed, Web of Science, Cochrane Library, and EMBASE databases were searched from the time of conception to June 2022 for randomized controlled trials (RCTs) investigating the use of IL-23 in PsA therapy. The main outcome of interest was the American College of Rheumatology 20 (ACR20) response rate at week 24. We included six RCTs (3 studies on guselkumab, 2 on risankizumab, and 1 on tildrakizumab) with a total of 2971 PsA patients in our meta-analysis. We found that the IL-23 inhibitor group showed a significantly higher ACR20 response rate compared to the placebo group (relative risk = 1.74, 95% confidence interval: 1.57–1.92; P < 0.001; I2 = 40%). There was no statistical difference in the risk of adverse events (P = 0.07) and serious adverse events (P = 0.20) between the IL-23 inhibitor and placebo groups. Notably, the rate of elevated transaminases in the IL-23 inhibitor group was higher than the placebo group (relative risk = 1.69; 95%CI 1.29–2.23; P < 0.001; I2 = 24%). In the treatment of PsA, IL-23 inhibitors significantly outperform placebo intervention while maintaining a favorable safety profile.

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IL-23 inhibition for the treatment of psoriatic arthritis

Cited by 12 publications

References 49 publications

Real‐life effectiveness and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: A 104‐week multicenter retrospective study – IL PSO (ITALIAN LANDSCAPE PSORIASIS)

Real‐life effectiveness and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: A 104‐week multicenter retrospective study – IL PSO (ITALIAN LANDSCAPE PSORIASIS)

Immune Checkpoint Inhibitors in Advanced Prostate Cancer: Current Data and Future Perspectives

Efficacy and safety of IL-23 inhibitors in the treatment of psoriatic arthritis: a meta-analysis based on randomized controlled trials

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