Autoreactivity to self-antigens LL37 and ADAMTSL5 influences the clinical response to risankizumab in psoriatic patients.

The autoantigens LL37 and ADAMTSL5 contribute to induce pathogenetic T-cells responses in a subset of psoriatic patients. Whether the presence of LL37-and/or ADAMTS5-reactive T-cells influences the clinical response to treatment is still unknown. The aim of the study is to evaluate the clinical responses to the anti-IL-23 risankizumab in LL37 and/or ADAMTSL5-reactive patients in comparison with non-reactive ones and to assess whether genetics (HLA-Cw06.02) or BMI influences the response to treatment. Patients were screened at baseline for the presence of circulating LL37 or/and ADAMTSL5-reactive T-cells and were treated as per protocol with risankizumab. Effectiveness data (PASI scores) were collected at weeks 4, 16, 28, 40 and 52. Data were also analyzed based on HLA-Cw06.02 status and BMI. The overall response to treatment of patients with autoreactivity to LL37 or ADAMTSL5 did not differ compared to the non-reactive cohort as measured as PASI75/90/100 at different time points; however, subjects that had autoreactive T-cells to both LL37 and ADAMTS5 demonstrated suboptimal response to treatment starting at week16. HLA-Cw06:02+ patients demonstrated faster response to risankizumab at week 4 compared to HLA-Cw06:02-. Additionally, the response to treatment was influenced by the BMI with slower responses seen in overweight and obese patients at week 4 and week16. In conclusion, while the presence of either LL37-and ADAMTS5-reactive circulating T-cells do not influence the clinical response to risankizumab, the presence of the double reactivity to both LL37 and ADAMTS5 decreases the clinical responses. Moreover, we evidenced that HLA-Cw06+ respond faster to IL-23 inhibition and that BMI, associated to autoreactivity, can influence the speed in response.

Upadacitinib for the treatment of concomitant psoriasis and atopic dermatitis: a case series.

Purpose: The overlap of psoriasis and atopic dermatitis (AD) is rare and treating moderate-to-severe cases can be challenging. Conventional immune-suppressive drugs cannot be used long-term, and no biological drugs are currently approved for treating both conditions.Method: We report the cases of four patients with overlapping features of both psoriasis and AD.Result: After being treated with several systemic drugs, including gold-standard treatments for both psoriasis and AD, they received upadacitinib 15 or 30 mg, achieving complete remission. Upadacitinib is an inhibitor of Janus Kinase 1, currently approved for treating moderate-to-severe AD.Conclusion: To date, very limited data are available regarding the efficacy of upadacitinib in psoriasis. In a phase-3 trial on the efficacy of upadacitinib 15 mg in patients affected by psoriatic arthritis, 52.3% of patients achieved a 75% improvement in Psoriasis Area and Severity Index (PASI75) after one year. Currently, no clinical trials are evaluating the efficacy of upadacitinib in plaque psoriasis.

Real-Life Effectiveness and Safety of Upadacitinib in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis: A Single-Center 16-Week Study.

INTRODUCTION: The treatment of severe atopic dermatitis (AD) includes cyclosporine and recently approved biologics and small molecules. Among these, upadacitinib is a selective inhibitor of Janus kinase 1, approved for the treatment of severe AD in adolescents/adults. Upadacitinib has shown efficacy and safety in several phase 3 clinical trials, but data on real-life patients are still lacking. METHODS: We conducted a retrospective real-life observational study to evaluate the effectiveness and safety of upadacitinib up to week 16 in a cohort of both bio-naïve and bio-experienced patients. This study was carried out by analyzing the AD database records of an Italian referral hospital. Thirty-eight patients were included in this study, and 35 completed 16 weeks of treatment. RESULTS: At week 16, out of 35 patients, the percentages of Eczema Area and Severity Index (EASI) 50, EASI 75, EASI 90 and EASI 100 responses were 94.29, 91.43, 74.29, and 60%, respectively. A decrease of at least 4 points from baseline of itch-NRS was reported by 94.74 and 91.43% of patients at weeks 8 and 16. Regarding the safety of upadacitinib, 26.32% of patients experienced at least one adverse event (AE), and a total of 13 AEs were recorded, including blood test abnormalities and papulopustular acne. None of our patients interrupted the drug because of an AE. CONCLUSIONS: We observed higher rates of EASI75/EASI90/EASI100 responses at week 16, compared with data from clinical trials. The safety profile of upadacitinib was favorable, as no AEs leading to discontinuation were experienced by our patients up to week 16.

Real-Life Effectiveness and Safety of Risankizumab in 131 Patients Affected by Moderate-to-Severe Plaque Psoriasis: A 52-Week Retrospective Study.

INTRODUCTION: Risankizumab is a humanized monoclonal antibody that selectively targets interleukin-23. It is approved for treatment of moderate-to-severe plaque psoriasis. We conducted a 52-week monocentric retrospective study to evaluate the effectiveness and safety of risankizumab in a real-life setting. METHODS: Our study included 131 adults with moderate-to-severe plaque psoriasis all treated with risankizumab for at least 52 weeks. Patient characteristics and PASI (Psoriasis Area and Severity Index) at each visit were recorded. The percentages of patients achieving 75%/90%/100% (PASI 75/90/100) improvement in PASI with respect to baseline were registered. RESULTS: At week 52, 93.9%, 78.6%, and 61.1% of patients achieved PASI 75/90/100, respectively. An absolute PASI ≤ 2 was reached by 90.8% at week 52. The higher body mass index and the presence of cardio-metabolic comorbidities did not interfere with the odds of reaching PASI 75/90/100 at each time-point. At week 52, comparable percentages of patients achieved PASI 100, regardless of the involvement of difficult-to-treat-areas. No significant safety findings were recorded and none of the patients had to interrupt the treatment because of adverse events. CONCLUSIONS: Our findings confirmed that risankizumab is a safe and effective therapeutic option for the treatment of a wide "real-life" cohort of patients with psoriasis.