Search

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]

A retrospective study conducted in Italy analyzed data from 116 patients with severe atopic dermatitis (AD) to determine if the drug upadacitinib could improve symptoms of concomitant allergic rhinitis (AR) or allergic asthma (AA). The study found that after 16 weeks of treatment with upadacitinib, 81.9% of patients achieved a reduction of at least 75% in their AD symptoms, and 56.03% achieved a reduction of at least 90%. Upadacitinib also showed a slight improvement in symptoms of AA and AR. The study suggests that upadacitinib may have a beneficial impact on AA and AR symptoms in patients with severe AD, but further research is needed. [Extracted from the article]

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]

Dear Editor, Dupilumab, an inhibitor of interleukin (IL)-4/13 activity, is a biological agent approved for the treatment of moderate-to-severe atopic dermatitis (AD).1 In this study, we aimed to assess the long-term effectiveness and safety of dupilumab in a real-world clinical setting. Primary effectiveness outcomes included the proportion of patients at week 52 achieving EASI improvements of 50%, 75% or 90% (EASI 50, EASI 75 or EASI 90). Laboratory safety of dupilumab in moderate-to-severe atopic dermatitis: results from three phase III trials (LIBERTY AD SOLO 1, LIBERTY AD SOLO 2, LIBERTY AD CHRONOS). [Extracted from the article]

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]

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]

Background: Moderate‐to‐severe atopic dermatitis (AD) in the adolescence is a high burden disease, and its treatment can be very challenging due to paucity of approved systemic drugs for this age and their side‐effects. Dupilumab was recently approved for treatment of adolescent AD. Objectives: A multicentre, prospective, real‐world study on the effectiveness and safety of dupilumab in adolescents (aged from ≥12 to <18 years) with moderate‐to‐severe AD was conducted. The main AD clinical phenotypes were also examined. Methods: Data of adolescents with moderate‐to‐severe AD treated with dupilumab at label dosage for 16 weeks were collected. Treatment outcome was assessed by EASI, NRS itch, NRS sleep loss and CDLQI scores at baseline and after 16 weeks of treatment. The clinical scores were also evaluated according to clinical phenotypes. Results: One hundred and thirty‐nine adolescents were enrolled in the study. Flexural eczema and head and neck eczema were the most frequent clinical phenotypes, followed by hand eczema and portrait‐like dermatitis. Coexistence of more than 1 phenotype was documented in 126/139 (88.5%) adolescents. Three patients (2.1%) contracted asymptomatic SARS‐CoV‐2 infection and 1 of the discontinued dupilumab treatment before the target treatment period. A significant improvement in EASI, NRS itch, NRS sleep loss and CDLQI was observed after 16 weeks of treatment with dupilumab. This outcome was better than that observed in clinical trials. Dupilumab resulted effective in all AD phenotypes, especially in diffuse eczema. Twenty‐eight (20.1%) patients reported adverse events, conjunctivitis and flushing being the most frequent. None of patients discontinued dupilumab due to adverse event. Conclusions: Dupilumab in adolescent AD showed excellent effectiveness at week 16 with consistent improvement of all clinical scores. Moreover, dupilumab showed a good safety profile also in this COVID‐19 pandemic era. [ABSTRACT FROM AUTHOR]

(b) Mean PASI reduction, relative PASI improvement, and residual PASI < 3 at weeks 12, 24, and 48 between obese and non-obese patients, PsA and non-PsA patients, and bio-naïve vs bio-experienced patients. Bio-naïve patients improved faster than bio-experienced patients in the first weeks of treatment and at every time point. Forty-nine patients reported side effects, the most frequent of which were arthralgia (15 patients) in patients without joint involvement at baseline and asthenia (10 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]

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]

Background: Treatment of moderate‐to‐severe atopic dermatitis (AD) in the elderly may be challenging, due to side‐effects of traditional anti‐inflammatory drugs and to comorbidities often found in this age group. Furthermore, efficacy and safety of innovative drugs such as dupilumab are not yet well known. Objectives: A multicentre retrospective, observational, real‐life study on the efficacy and safety of dupilumab was conducted in a group of patients aged ≥65 years and affected by severe AD. Their main clinical features were also examined. Methods: Data of elderly patients with severe (EASI ≥24) AD treated with dupilumab at label dosage for 16 weeks were retrospectively collected. Treatment outcome was assessed by comparing objective (EASI) and subjective (P‐NRS, S‐NRS and DLQI) scores at baseline and after 16 weeks of treatment. Results: Two hundred and seventy‐six patients were enrolled in the study. They represented 11.37% of all patients with severe AD. Flexural eczema was the most frequent clinical phenotype, followed by prurigo nodularis. The coexistence of more than one phenotype was found in 63/276 (22.82%) subjects. Data on the 16‐week treatment with dupilumab were available for 253 (91.67%) patients. Efficacy of dupilumab was demonstrated by a significant reduction of all the scores. No statistically significant difference regarding efficacy was found in elderly patients when compared to the group of our AD patients aged 18–64 years, treated with dupilumab over the same period. Furthermore, only 18 (6.52%) patients discontinued the drug due to inefficacy. Sixty‐one (22.51%) patients reported adverse events, conjunctivitis and flushing being the most frequent. One (0.36%) patient only discontinued dupilumab due to an adverse event. Conclusions: Therapy with dupilumab led to a significant improvement of AD over a 16‐week treatment period, with a good safety profile. Therefore, dupilumab could be considered as an efficacious and safe treatment for AD also in the elderly. [ABSTRACT FROM AUTHOR]

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]

I Dear Editor i , Recently, dupilumab, an anti-IL-4R antibody, has become available for the treatment of moderate-to-severe atopic dermatitis (AD).1-4 Baseline patient characteristics that can be used as predictors of response to dupilumab treatment in AD patients have not yet been identified. In conclusion, this study highlights that specific baseline patient characteristics may help to predict treatment outcomes and the time of a complete response to dupilumab in AD. [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]

Globally, <5 years have passed between cancer diagnoses and the starting of dupilumab for six out of seven patients with a cancer history; four of them already have a significant follow-up time beyond 1 year (for patients no. 1, 3, 5 and 6). Data regarding the association between atopic dermatitis (AD) and specific tumours are still controversial.1-3 Conflicting data have also been reported about the involvement of Interleukin (IL)-4 and IL-13 in carcinogenesis.4 We report our experience relating to both the use of dupilumab in patients with a previous history of cancer and the onset of tumour in patients receiving dupilumab. Most of the patients had long-lasting skin disease, and two patients had undergone cyclosporine treatment prior to cancer diagnosis. [Extracted from the article]

Background: The clinical features and the prognostic relevance of vitiligo lesions in melanoma patients are still controversial. This prospective observational study was designed to characterise the clinical features of melanoma-associated vitiligo, to analyse the association with other autoimmune manifestations and to ascertain whether the development of vitiligo lesions carries a prognostic relevance on the clinical course of melanoma. Materials and methods: A total of 2954 consecutive patients have been included; multivariate analyses of distant metastasis-free survival (DMFS) and overall survival (OS) were carried out to ascertain the independent prognostic role of vitiligo as a time-dependent covariate. Results: Vitiligo was demonstrated in 83 of 2954 melanoma patients (2.8%). A significantly higher percentage of autoimmune diseases was demonstrated in vitiligo patients (7 of 83) with respect to patients without vitiligo (80 of 2871) (P = 0.004). Multivariate analyses selected the time-dependent covariate vitiligo as the favourable independent prognostic variable associated to a longer DMFS in stage III and a higher OS in both stage III and stage IV. Conclusion: Melanoma-associated vitiligo should be considered as a distinct clinical entity, separate from vitiligo vulgaris, and identifies a subgroup of patients characterised by a high prevalence of immune-mediated diseases and by a favourable prognosis. [ABSTRACT FROM AUTHOR]

Median canaliform nail dystrophy of Heller in a patient with atopic dermatitis: "miraculous" healing with dupilumab Median canaliform dystrophy of Heller is a relatively rare nail abnormality characterized by central single longitudinal split with an inverted fir-tree pattern, which commonly involves the thumbnails, and rarely other fingernails.[1] The pathogenesis is not entirely clear; the most common hypothesis is repetitive trauma to the proximal nail fold and the underlying nail matrix, also self-induced, or compression by subungual tumours. We report a patient in whom nail dystrophy resolved following resolution of pruritus with dupilumab, given for severe AD. [Extracted from the article]

The aim of this study is to define the relationship between the tyrosinase expression in the peripheral blood and the clinical course of the disease in stage III disease-free melanoma patients after radical lymph node dissection. RT-PCR techniques were used to identify tyrosinase mRNA in 110 patients; a total of 542 blood samples were investigated. In all, 54 patients (49%) showed at least one positive result; 13 patients (11.8%) showed baseline positive results: six became negative thereafter, whereas seven showed follow-up positive results until disease progression occurred. One or more positive determinations were found during follow-up in 41 patients with negative baseline tyrosinase. No correlation was found between baseline results and the relapse rate or disease-free survival (DFS), whereas a significant correlation was found between positive tyrosinase results and disease recurrence during follow-up. In fact, 72.9% of positive patients relapsed, but only 19.3% of negative cases did so. The median interval between the positive results and the clinical demonstration of the relapse was 1.9 months (range 1-6.6). Disease-free survival multivariate analysis selected, as independent variables, Breslow thickness (P=0.05), lymph node involvement according to the AJCC classification (P=0.05) and tyrosinase expression (P=0.0001). In conclusion, RT-PCR tyrosinase mRNA expression is a reliable and reproducible marker associated with a high risk of melanoma progression and we encourage its clinical use in routine follow-up. [ABSTRACT FROM AUTHOR]