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Introduction: Ixekizumab proved to be effective and safe for psoriasis treatment in several randomized clinical trials and real‐life studies. Nevertheless, long‐term real‐world experiences are still lacking, with little data up to 4 years of treatment. Objectives: To analyse survival, effectiveness and safety of ixekizumab in a real‐life cohort of patients affected by moderate‐to‐severe psoriasis or psoriatic arthritis up to 260 weeks (5 years). Methods: We included all patients treated with ixekizumab from December 2017 to March 2021. Drug survival (DS) was analysed in patients at risk for up to 5 years. Cox analysis was adopted to evaluate possible predictive factors of discontinuation. Psoriasis Area Severity Index (meanPASI and PASI100, 90, and ≤3) was used as outcomes of effectiveness on observed patients at 16, 52, 104, 156, 208 and 260 weeks. Logistic regression was performed to identify possible predictive factors of response. Results: DS was 65.5% at 260 weeks, with being a super‐responder patient (achievement of PASI100 at 16 weeks and maintained at 28 weeks) correlated with less risk of discontinuation. PASI100, 90 and ≤3 was achieved by 54.1%, 60.5% and 73% of observed patients, respectively, at 16 weeks, and by 59.1%, 81.8% and 95.5%, respectively, at 260 weeks. High mean BMI was the only factor strongly associated with less achievement of the outcomes at the earlier time points: PASI100 at 16 weeks (OR 0.93, CI 0.87–0.98, p = 0.014) and at 104 weeks (OR 0.91, CI 0.84–0.98, p = 0.019), PASI90 achievement at 16 weeks (OR 0.94, CI 0.88–0.99, p = 0.028) and 104 weeks (OR 0.91, CI 0.83–0.99, p = 0.027), and PASI ≤3 (OR 0.86, CI 0.76–0.97, p = 0.018) at 104 weeks. No severe adverse events were observed. Conclusions: Ixekizumab showed high effectiveness and safety for up to 5 years, with survival of 2/3 of treated patients. Rapid response to treatment is predictive of long‐term response. [ABSTRACT FROM AUTHOR]

Background: Many national guidelines at the European level recommend first‐line therapy based on the anti‐TNF‐alpha adalimumab for treatment of psoriasis and psoriatic arthritis, mainly for economic reasons. Consequently, patients being treated with newer IL‐17 and IL‐23 inhibitors underwent previous unsuccessful first‐line adalimumab‐based therapy. Objectives: Evaluate the efficacy and safety of IL‐17 and IL‐23 inhibitors after treatment with adalimumab compared to adalimumab‐naive psoriatic patients. Methods: We retrospectively analysed 1053 psoriatic patients treated with anti‐IL17 and anti‐IL23 agents, which included 68 and 24 adalimumab‐experienced and 399 and 260 bio‐naive patients. Efficacy was assessed with mean PASI, PASI90, PASI100, and <3. Results: Concerning the achieving of PASI100, PASI90 and PASI < 3 in patients treated with anti‐IL17 agents, no significant differences were observed between adalimumab‐experienced and bio‐naive patients. In patients treated with an anti‐IL‐23 agent, a faster response was observed in bio‐naive patients, with PASI < 3 significantly higher than ADA‐experienced patients at 16 weeks (77% vs. 58% p = 0.048). In a sub‐analysis that evaluated the performance of anti‐IL17 and anti‐IL23 agents in adalimumab‐experienced patients with a history of secondary failure, no significant differences were found. In multivariate analysis of PASI100, only anti‐IL‐17 therapy appeared to have a negative impact at 52 weeks (OR: 0.54 p = 0.04) independently of previous treatment. For PASI90, type of treatment and bio‐naïve status did not seem to have an impact at any time point. Conclusions: Anti‐IL 23 and anti‐IL 17 agents are not significantly different in terms of efficacy in bio‐naive patients or as second‐line therapy after failure with a biosimilar or originator adalimumab. [ABSTRACT FROM AUTHOR]

Importance: Primary cutaneous lymphomas (PCL) are rare diseases, but the indolent course makes their prevalence high. Although there are many treatment options, no hierarchy is recommended. Objective: To identify the burden of PCL and describe clinical‐pathologic features; associated comorbidities; analyse treatment approaches in real‐life and the parameters associated with the achievement of complete response (CR). Design, setting and participants: In this study, all the PCL patients (384 patients) consecutively seen at the Dermatologic Clinic of the University of Turin from January 1, 2019 to December 31, 2019, with follow‐up updated to December 2020, were included. Main outcomes and measures: Subtype of PCL, demographic data, time elapsed between first lesions and diagnosis, associated symptoms, comorbidities, staging at diagnosis, high‐grade transformation, blood involvement, stage progression, therapies used and response were assessed. Results: 247 were cutaneous T‐cell lymphomas (CTCL, 64.3%), 137 cutaneous B‐cell lymphomas (CBCL, 35.7%) and the most frequent subtype was MF (48.4%). 62.3% of CTCL patients showed at least one comorbidity, mainly cardiovascular (28.7%), 20.2% show other not cutaneous neoplasms. The main approaches were skin‐directed therapies (topical steroids 65.6%; phototherapy 50.2%). 39.3% patients achieved a CR during the disease course. Pruritus, the presence of comorbidities and high‐grade transformation were factors associated with failure to achieve CR, whereas stage IA of MF was associated with greater achievement of CR. Conclusions and relevance: The Th2 cytokine related development of pruritus could justify increased resistance to treatment, while the presence of associated comorbidities could reduce treatment options as well as treatment compliance. [ABSTRACT FROM AUTHOR]

This is because bio-naïve patients are candidates for biological treatment with a higher PASI than bio-experienced patients who have taken risankizumab following initial secondary inefficacy. Bio-experienced patients achieved PASI90 less than bio-naïve (40.41% vs. 55%, I P i = 0.041) at 16 weeks, differences was also detected in PASI90, 75 and PASI < 3 at week 28 between the two populations (65% vs. 84%, 77% vs. 93% and 78% vs. 91%, I P i = 0.003, I P i = 0.001 and I P i = 0.011 respectively). Effect of Risankizumab on patient-reported outcomes in moderate to severe psoriasis: the UltIMMa-1 and UltIMMa-2 randomized clinical trials. [Extracted from the article]

Keywords: biologics; comorbidities; frail patients; PASI; psoriasis EN biologics comorbidities frail patients PASI psoriasis 1162 1164 3 07/14/23 20230701 NES 230701 DATA AVAILABILITY STATEMENT The data that support the findings of this study are available on request from the corresponding author. In this analysis, we clustered patients into two groups: patients who reported at least one comorbidity at the time of the diagnosis (219, 78.21%) and those who denied comorbidities (61, 21.79%). The most represented comorbidities were hypertension (105 patients), type 2 diabetes mellitus (32 patients), dyslipidaemia (26 patients), acute ischemic cardiopathy (25 patients), COPD (13 patients), symptomatic benign prostatic hyperplasia (19 patients), arthrosis (11 patients), HCV (nine patients), asthma (five patients) and other (81 patients). [Extracted from the article]

The atopic patient also suffers from non-allergic comorbidities whose impact on response to systemic treatments has rarely been evaluated in clinical practice.3 Among these, data on the impact of metabolic and psychiatric comorbidities in the response to dupilumab are scarce. Impact of comorbidities in the response of atopic patients treated with dupilumab: a real-life study up to 36 weeks 19 patients have no comorbidity at baseline vs. 22, this difference was not significant ( I P i = 0.5), similar results were observed when considering only patients with allergic comorbidities ( I P i = 0.22). [Extracted from the article]

This article is a response to a letter by Dr. Yu and Cheng-Chun Wei regarding the efficacy of anti-IL-23 and anti-IL-17 treatments after adalimumab failure in psoriatic patients. The authors agree with the lack of real-life studies comparing the rapidity of action and drug survival between IL-17 and IL-23 inhibitors. They provide data suggesting a higher survival rate for IL-23 inhibitors compared to TNF alpha inhibitors and IL-17 inhibitors. The authors also acknowledge the need for studies on the prevention of psoriasis-associated comorbidities and the inclusion of diverse ethnic groups in research. However, they note that their study was conducted in a university hospital in Northern Italy and had limited representation of non-Caucasian populations. They encourage researchers in other countries to share their experiences to better understand the response to biological treatments in different ethnic groups. [Extracted from the article]

These results were maintained at week 24, showing a higher rate of patients achieving PASI 90, PASI < 3 and PASI 100 responses in the ixekizumab group. A statistically significant difference was observed at week 48, where PASI 90, PASI < 3 and PASI 100 response rates were achieved by 4 (31%), 6 (46%) and 3 (23%) in the secukinumab group; and 4 (100%), 4 (100%) and 3 (75%) in the ixekizumab group respectively. In the PP group, the outcomes at 12 weeks showed that ixekizumab is faster than secukinumab in achieving PASI 90, PASI < 3 and PASI 100, yet without achieving statistically significant difference: a PASI 90 response was achieved by 29% of patients treated with secukinumab and 50% of patients treated with ixekizumab, while a PASI 100 response was achieved in the two groups by 29% and 33% of patients respectively. At week 48, a statistically significant difference in achieving PASI 90, PASI < 3 and PASI 100 response (100%, 100% and 75% of patients treated with ixekizumab achieved PASI 90, PASI < 3 and PASI 100, vs. 31%, 46% and 23% of patients treated with secukinumab respectively) was observed ( I P i = 0.01; Fig. [Extracted from the article]

Ixekizumab showed significantly higher efficacy in terms of PASI 90 at week 24, and a higher superiority of PASI 90 and PASI 100 also at week 48. In bio-naive patients, we found a significantly higher rate of PASI-90, PASI < 3 and PASI-100 with ixekizumab compared to the secukinumab ( I P i < 0.05), while in bio-experienced patients no significant difference was observed. There was no difference between the two drug survival curves among the two treatment arms. gl PASI-90 and PASI-100 response rates were achieved at week 12 by 124 (48%) and 108 (42%) in the secukinumab group ( I P i = 0.001), while 118 (64%) and 100 (54%) in the ixekizumab group ( I P i = 0.014) respectively (Figure 1b). [Extracted from the article]

This letter to the editor discusses the case of a 52-year-old female patient with atopic dermatitis (AD) who experienced treatment failure with various medications. The patient initially tried dupilumab, which improved some symptoms but did not fully resolve the condition. She then switched to upadacitinib, which initially showed improvement but later led to worsening symptoms and side effects. Finally, the patient started tralokinumab, which resulted in some initial improvement but persistent facial involvement. The letter highlights the challenges of treating resistant AD and suggests that more research is needed to identify factors that contribute to treatment resistance. [Extracted from the article]