Treatment of severe atopic dermatitis with tralokinumab in clinical practice: short-term effectiveness and safety results.

BACKGROUND: Tralokinumab was recently approved for the treatment of moderate-to-severe atopic dermatitis (AD) and is the first selective interleukin (IL)-13 inhibitor that specifically neutralizes IL-13 with high affinity. OBJECTIVES: To determine the real-life short-term effectiveness and safety of tralokinumab treatment in patients with moderate-to-severe AD. METHODS: A multicentre retrospective study was conducted including adult patients with moderate-to-severe AD who started tralokinumab treatment from 1 April to 30 June 2022 in 16 Spanish hospitals. Demographic and disease characteristics, severity and quality of life scales were collected at the baseline visit and at weeks 4 and 16. RESULTS: Eighty-five patients were included. Twenty-seven patients (32%) were non-naive to advanced therapy (biological or Janus kinase inhibitors inhibitors). All included patients had severe disease with baseline Eczema Area and Severity Index (EASI) scores of 25.4 (SD 8.1), Dermatology Life Quality Index (DLQI) 15.8 (5.4) and peak pruritus numerical rating scale (PP-NRS) 8.1 (1.8) and 65% had an Investigator's Global Assessment (IGA) of 4. At week 16, there was improvement on all scales. The mean EASI decreased to 7.5 (SD 6.9, 70% improvement), SCORing Atopic Dermatitis improved 64% and PP-NRS, 57%. Also, 82%, 58% and 21% of the patients achieved EASI 50, 75 and 90, respectively. The percentage of EASI 75 responders was significantly higher among the naive vs. non-naive groups (67% vs. 41%). The safety profile was acceptable. CONCLUSIONS: Patients, with a long history of disease and prior multidrug failure, showed a good response to tralokinumab, confirming clinical trial results.

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.

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.

Guselkumab: Mid-term effectiveness, drug survival, and safety in real clinical practice.

Guselkumab is a fully human immunoglobulin-G1-lambda (IgG1λ) monoclonal antibody that binds selectively to the p19 subunit of interleukin 23. Few series of real clinical practice that reflect the use of guselkumab have been published so far, including the measure of survival at more than 52 weeks. An observational, longitudinal, retrospective study of real clinical practice of patients with moderate to severe psoriasis receiving treatment with guselkumab 100 mg subcutaneous every 8 weeks in five tertiary hospitals in Andalusia (Spain) was carried out. A total of 87 patients were included in this study. Disease severity and treatment response was assessed by PASI, BSA, VAS pruritus, and DLQI at baseline and after 4, 12, 24, 36, 52, and 76 weeks. Data are presented as mean ± SD for continuous variables, and number and percentage for categorical variables. To determine the differences between visits in PASI, BSA, VAS pruritus, and DLQI a Wilcoxon matched-pairs test was performed. The survival of guselkumab was calculated using Kaplan-Meier survival analysis. Our population presented with a mean age of 49.9 years, 60.9% of them were male, had a mean PSO evolution of 20.4 (9.5) years. A total of 79.3% were obese or presented with overweight and had several comorbidities (dyslipidemia 28.7%, arterial hypertension 23% and 20% diabetes among others). At baseline their disease parameters were: PASI = 14.6 (7.2), BSA = 22.3 (16.6), VAS pruritus = 6.0 (2), and DLQI = 15.8 (5). After 52 weeks their disease improved to PASI = 0.9 (1.1), BSA = 1.0 (1.8), VAS pruritus = 0.47 (0.88), and DLQI = 1.54 (2.50). The percentage of patients who achieved PASI 75, 90, and 100 at 52 weeks was 90.3%, 71%, and 51.6%, respectively. The patients evaluated at week 76 (n = 3) reached PASI 0, BSA 0, and DLQI 0. After 93.4 weeks (1 year, 9 months, and 14 days), the overall survival rate was 94% (4 events were reported). A total of four patients discontinue to AE or lack of efficacy after 76 weeks. Guselkumab showed excellent results in the control of psoriasis in the mid-term with an elevated number of patients maintaining treatment after 52 to 76 weeks and a good safety profile.

Prevalence of chronic urticaria refractory to antihistamines in Andalucia, Spain.

Chronic urticaria (CU) has a devastating effect on the quality of life of patients who suffer from it. The objective of this study is to determine the prevalence of severe chronic spontaneous urticaria (CSU) in adults in eight health areas in Andalucía. A retrospective observational study from January 2019 to December 2019 was conducted with the participation of seven reference hospitals that were analyzed, including a total reference population of 3 159 001 individuals ≥18 years. The analysis was carried out on the characteristics of the population and the estimated prevalence. In total, 369 patients with a diagnosis of CSU refractory to antagonist of histamine were registered. We have found a prevalence of refractory patients of 0.0012% (95% CI 0.0010%-0.0013), ranging from 0.006% to 0.02%. The present study has helped to describe the prevalence and characteristics of patients with severe urticarial. The prevalence is lower than previously reported. We have observed differences between hospital areas. There will be a new line of research at the national level to help improve the identification of patients with CSU.

Development and validation of a questionnaire to measure empowerment in adult patients with atopic dermatitis. The DATEMP questionnaire.

BACKGROUND AND OBJECTIVES: In recent years, the hypothesis that increasing the empowerment of patients can help to improve health outcomes and rationalize the use of health services has become relevant, especially for chronic diseases. Developing validated measurement tools is necessary to achieve this goal. In the field of dermatology, there are few studies related to empowerment of the patient. The aim of the present research is to develop and validate a self-administered questionnaire for adult patients diagnosed with atopic dermatitis (AD) in order to measure their level of empowerment. METHODS: After a literature review and the establishment of consulting groups of patients and dermatologists, a large battery of 35 items was generated, based on the dimensions included in previous empowerment descriptions. A multidisciplinary group selected the 20 most suitable items to include in the questionnaire. A cross-sectional study was carried out with the items included in the questionnaire as well as demographic and clinical characteristics. To reduce the number of items and measure the construct validity, an exploratory factorial analysis (EFA) of the primary components and varimax rotation were used. Cronbach's α was used to measure the reliability of the individual scales and the global questionnaire. RESULTS: 242 valid questionnaires were included. After completion of the EFA, the final Dermatitis Atópica EMPoderamiento (DATEMP) questionnaire was composed of 17 items that converged on four factors. The four scales had adequate reliability: "Knowledge" (Cronbach's alpha = 0.808), "Abilities" (Cronbach's alpha = 0.744), "Intention to change" (Cronbach's alpha = 0.798) and "Coping skills" (Cronbach's alpha = 0.772). The overall Cronbach's α of the questionnaire was 0.764. CONCLUSIONS: The DATEMP questionnaire is the first specific empowerment measurement instrument developed for patients with AD that has demonstrated adequate levels of reliability and construct validity. It is a self-administered questionnaire that is simple and quick to answer.

Histological Features, p53, c-Kit, and Poliomavirus Status and Impact on Survival in Merkel Cell Carcinoma Patients.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive malignancy from neuroendocrine cells in the skin. Despite being one of the most life-threatening of skin cancers, little is known about the potential signaling mechanism that drives carcinogenesis in MCC. The purpose of this study is to assess the impact of Merkel cell polyomavirus (MCPyV), p53, and c-kit on the histological features and clinical prognosis of MCC treated in our regional hospitals. METHOD: The design was a retrospective study. The specimens were taken between 1993 and 2013 in 2 referral hospitals of Southern Spain. Data were collected retrospectively and analyzed using SPSS software. RESULTS: Thirteen lesions from 13 subjects were included in the study. Positivity for c-kit was associated with the absence of MCPyV viral DNA (P = 0.048) and positivity for p53 (P = 0.002). More rate of mitoses per high-power field was presented significantly in those specimens with: positivity for c-kit (P = 0.046), positivity for p53 (P = 0.05), lesions with infiltrative growth pattern (P = 0.008), and lymphovascular invasion (P = 0.034). We observed an inverse relationship between p53 expression and MCPyV infection (Pearson's coefficient: -0.524; P = 0.046) and between c-kit expression and MCPyV infection (Pearson's coefficient: -0.548; P = 0.05), whereas the relationship was positive between p53 expression and c-kit expression (Pearson's coefficient: 0.884; P < 0.001). CONCLUSION: We conclude that presence of MCPyV DNA has no effect on overall survival. MCCs with p53 and c-kit expressions are associated with the absence of or low MCPyV DNA showing an inverse relationship. A multifactorial molecular pathogenesis where positivity for p53 and c-kit are associated with other mechanisms different than MCPyV (such as pro-mitotic factors) may lead to aggressive clinical behavior.

Verrucous tumor mimicking squamous cell carcinoma in immunocompetent patient.

Mycobacteria cause a range of diseases in both immunocompetent and immunosuppressed individuals. An increase in non-tuberculous mycobacterial (NTM) infections targeting skin has been described. Many hypotheses have been developed in order to explain it: the increasing burden of immunocompromised individuals, immigration from endemic countries, improved laboratory identification techniques, and changes inhuman behavior that expose individuals to this NTM. Mycobacterium mucogenicum group comprises M. mucogenicum, Mycobacterium aubagnense, and Mycobacterium phocaicum. This group of organisms was first named Mycobacterium chelonae-like organism in 1982. Most clinically significant cases of those organisms involved catheter-related infections. Nevertheless, we report an interesting patient with a cutaneous infection produced by M. mucogenicum mimicking a squamous cell carcinoma; an excellent response to combined therapy with rifampicin and clarythromicin was observed.

Real-World Clinical Experience of Dupilumab in the Treatment of Chronic Palmo-Plantar Eczema in Patients with Moderate-Severe Atopic Dermatitis: 52-Week Follow-Up.

Background: Hand-foot eczema (HFE) are special locations of dermatitis, which are often associated with atopic dermatitis (AD) and have a significant negative impact on the quality of life, demanding a clinically relevant improvement. Objectives: To evaluate the effectiveness and safety of dupilumab in the treatment of eczema localized in hands and/or feet in patients with moderate-to-severe AD. Methods: Retrospective multicenter study of adult patients with HFE treated with dupilumab for their AD. Patients with other concomitantly systemic immunosuppressive treatments did not undergo a washout period. The severity of palmar and/or plantar involvement was assessed using the Physician Global Assessment (PGA) scale on a scale of 0 ( = clear) to 5 ( = very severe). Eczema Area and Severity Index (EASI) and NRS-pruritus scales were also evaluated. One hundred percent of patients reached week 16, while 67/84 reached week 52 of follow-up. Results: A total of 84 patients were included 86.69% of patients showed a reduction in PGA-Hand, and 80.34% in PGA-Foot at week 52, EASI improvement was reached by 83.55% of patients at week 16 and 87.35% at week 52. Reduction of pruritus (≥4 points in NRS-pruritus scale) was 73.01% at week 16 and 80.67% at week 52. No differences in response to dupilumab were observed in the different subtypes of palmo-plantar dermatitis. Conclusions: The results obtained in our study suggest that dupilumab may be an effective and safe therapeutic option for the treatment of dermatitis localized in hands and/or feet.

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.

Brodalumab: Efficacy, safety, and survival in mid-term (52 weeks) on real clinical practice in Andalucia, Spain.

INTRODUCTION: Brodalumab is a recombinant monoclonal antibody (IgG2) that binds with high affinity to the human interleukin-17 (IL-17) receptor A and blocks the biological activity of the proinflammatory cytokines IL-17A, IL-17F, IL-17A/F heterodimer, and IL- 25, resulting in inhibition of inflammation and clinical symptoms associated with psoriasis. Its introduction has managed to increase the levels of efficacy, safety (improving that previously presented by the anti-IL-17 class), and survival. 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 brodalumab. This cross-sectional analysis includes information of patients between February 2019 and February 2022. A total of five tertiary hospitals in Andalusia (Spain) participated in this study. Analyses were performed "as observed" using GraphPad Prism version 8.3.0 for Windows. RESULTS: Our study included 85 patients, 54 men (63.5%) and 31 women (36.5%), with moderate-severe psoriasis treated with brodalumab. In order to evaluate the efficacy of brodalumab, our patients started with mean Psoriasis Area and Severity Index (PASI) values of 12.8 and body surface area (BSA) of 16.9, as well as a Dermatology Life Quality Index (DLQI) of 15.6, highlighting that they reported that the mean baseline visual analog scale (VAS) pruritus was 6.15. On week 52, mean PASI reached 1.26 and mean BSA 2.3, showing a clear stabilization and even sustained improvement regarding results on week 12. Concerning the brodalumab survival, we obtained 85.8% persistence at week 52. DISCUSSION: Brodalumab 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 brodalumab between patients coming from previous therapies.

Upadacitinib for moderate to severe atopic dermatitis.

Atopic dermatitis is an inflammatory skin disease, the prevalence of which has increased in the last decade. It affects all age groups, with adult involvement being a major focus of interest in recent years. The unmet needs of the disease, such as pruritus, sleep quality impairment and eczematous skin lesions, have undergone a therapeutic revolution following the commercialization of drugs such as JAK inhibitors. Upadacitinib, a selective JAK1 inhibitor, has been positioned by both clinical trial results and those observed in clinical practice as the fastest and most effective drug in reducing both pruritus and Eczema Area and Severity Index and validated Investigator Global Assessment. Although the safety profile may be initially alarming, it is advisable to update the actual data in this regard for proper management. New perspectives for upadacitinib in nonatopic comorbidities such as psoriasis and alopecia areata are beginning to be described, and interest in learning more about its peculiarities is growing.

Atopic dermatitis is the most common inflammatory skin disease. The inflammation happens when the body's defense system attacks the body's tissue. People with atopic dermatitis often have itching and red and scaly parts of the skin. The inflammation tends to be long-lasting and comes back repeatedly. The main goal of treatment is controlling the inflammation, which occurs because of a certain group of proteins called cytokines. Receptors called JAKs are involved in the inflammation that happens through cytokines, so they play an important role in this disease. A medicine called upadacitinib has been approved for the treatment of moderate to severe atopic dermatitis. In this article, you will find the most relevant published information on upadacitinib, including how effective and safe the medicine is based on both clinical studies and real-life cases.

Multicenter Retrospective Andalusian Study of the Use of Sonidegib for the Treatment of Local Advanced Basal Cell Carcinoma in Real Clinical Practice.

INTRODUCTION: Locally advanced basal cell carcinoma (LA-BCC) is defined as that BCC in which there is radiological confirmation of invasion of certain neighboring structures in depth and also, usually, a BCC that is of a sufficient size and invasion (although there is no radiological demonstration of deep invasion) in which surgery and radiotherapy are not adequate, are insufficient or are contraindicated to achieve the cure of the tumor, either due to characteristics of the tumor itself or of the patient. Sonidegib is indicated for the treatment of adult patients with locally advanced basal cell carcinoma that is not amenable to curative surgery or radiotherapy. MATERIAL AND METHODS: This is a retrospective, multicenter and descriptive study in nine centers in Andalusia, Spain. Patients treated with sonidegib for >3 months for locally advanced BCC were included from 1 January 2021 to 1 January 2023. Epidemiological, efficacy and safety data were collected. RESULTS: In the present study, a total of 38 patients were included, with a median age of 76.23 years (range 40-101). Prior treatment was surgery (31.57%; n = 25), radiotherapy (15.78%; n = 6), vismodegib (31.57%; n = 12). Eleven patients had not received prior treatment. LA-BCC were located in the cephalic pole, face or scalp. There was a total response in 9/38 patients (23.7%), partial response in 25/38 patients (65.8%) and no response in 4 patients (10.52%). In 6/34 patients, the dose was reduced to 200 mg every other day until it was discontinued due to adverse effects. The main adverse effects reported were dysgeusia (n = 8), asthenia (n = 8), = 6), muscle spasms (n = 6), alopecia (n = 4) and gastrointestinal intolerance (n = 4). DISCUSSION: Sonidegib is the second iHh authorized for the treatment of adult patients with locally advanced BCC who are not amenable to curative surgery or radiotherapy, based on the results of the phase II clinical trial, BOLT. Sonidegib shows good effectiveness and an acceptable safety profile in routine clinical practice in the sample presented.

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.