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A key challenge in psoriasis therapy is the tendency for lesions to recur in previously affected anatomical locations after treatment discontinuation following lesion resolution. Available evidence supports the concept of a localized immunological 'memory' that persists in resolved skin after complete disappearance of visible inflammation, as well as the role of a specific subpopulation of T cells characterized by the dermotropic CCR4

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PDF file - 68K, Survival of ICOS+ but not ICOS- T regulatory cells are dependent on ICOS-L provided by plasmacytoid dendritic cells. ICOS+ and ICOS- T regulatory cells isolated from peripheral blood of healthy volunteers were co-cultured with or without autologous plasmacytoid dendritic cells in the presence or absence of neutralizing anti-ICOS-L antibodies as described. Data depicted represent numbers of viable cells after four days of culture. Representative experiment of at least three independent experiments is shown. pDC = plasmacytoid dendritic cells, Treg = T regulatory cells

PDF file - 54K, Plasmacytoid dendritic cells do not correlate with ICOS- Foxp3+ T regulatory cells in the tumor microenvironment. Percentages of plasmacytoid dendritic cells (pDC) and percentages of ICOS- Foxp3+ T regulatory cells as analyzed by FACS show no correlation within the tumor microenvironment of ovarian cancer

Epithelial ovarian cancer (EOC) is the fifth most common cause of cancer death among women. Despite its immunogenicity, effective antitumor responses are limited, due, in part, to the presence of forkhead box protein 3–positive (Foxp3+) T regulatory (Treg) cells in the tumor microenvironment. However, the mechanisms that regulate the accumulation and the suppressive function of these Foxp3+ Treg cells are poorly understood. Here, we found that the majority of Foxp3+ Treg cells accumulating in the tumor microenvironment of EOCs belong to the subset of Foxp3+ Treg cells expressing inducible costimulator (ICOS). The expansion and the suppressive function of these cells were strictly dependent on ICOS-L costimulation provided by tumor plasmacytoid dendritic cells (pDC). Accordingly, ICOS+ Foxp3+ Treg cells were found to localize in close vicinity of tumor pDCs, and their number directly correlated with the numbers of pDCs in the tumors. Furthermore, pDCs and ICOS+ Foxp3+ Treg cells were found to be strong predictors for disease progression in patients with ovarian cancer, with ICOS+ Treg cell subset being a stronger predictor than total Foxp3+ Treg cells. These findings suggest an essential role for pDCs and ICOS-L in immunosuppression mediated by ICOS+ Foxp3+ Treg cells, leading to tumor progression in ovarian cancer. Cancer Res; 72(20); 5240–9. ©2012 AACR.

Background BE SURE 1-year results demonstrated the superior efficacy of bimekizumab compared with adalimumab with no unexpected safety findings. Objectives To provide efficacy and safety data over 2 years of bimekizumab treatment compared with adalimumab from BE SURE and the BE BRIGHT open-label extension (OLE) in patients with moderate-to-severe plaque psoriasis. Methods The 56-week double-blinded BE SURE phase III randomized controlled trial randomized patients 1 : 1 : 1 to bimekizumab 320 mg every 4 weeks (Q4W), bimekizumab 320 mg Q4W to week 16 then every 8 weeks (Q8W), or adalimumab 40 mg every 2 weeks to week 24 then bimekizumab 320 mg Q4W. After completing BE SURE, patients could enter the ongoing BE BRIGHT OLE, with possible dosing adjustments based on Psoriasis Area and Severity Index (PASI). The primary outcome in BE BRIGHT was incidence of treatment-emergent adverse events (TEAEs); safety data are reported by study period through week 104. Efficacy data are reported for the intention-to-treat population through week 104 by initial randomization group, with ≥ 90% improvement from baseline PASI (PASI 90) and 100% improvement (PASI 100) as key outcomes. Results Of the patients randomized to bimekizumab, 158 were assigned to Q4W, and 161 to Q4W/Q8W. At week 104, PASI 90 was achieved by 91.2% and 89.7%, and PASI 100 was achieved by 72.3% and 68.1%, for Q4W and Q4W/Q8W, respectively; comparable to week 16 results. Among the 159 patients randomized to adalimumab, responses rapidly and substantially increased after the week 24 bimekizumab switch; at week 104, 96.9% and 70.2% of patients achieved PASI 90 and PASI 100 respectively. Through weeks 24–104, the three most common TEAEs in any bimekizumab-treated group were nasopharyngitis, oral candidiasis and upper respiratory tract infection. Rates of serious TEAEs were low. Conclusions Clinical responses observed through week 16 of BE SURE in patients randomized to bimekizumab were sustained through 104 weeks of treatment, regardless of Q4W or Q8W maintenance dosing. Response rates were also sustained through week 104 in patients who switched from adalimumab to bimekizumab at week 24, and were similar to those observed in the bimekizumab groups. Bimekizumab was well tolerated with no new safety signals.

Manifestations of psoriasis in special areas are difficult to treat and are associated with a high disease burden and significant quality of life (QoL) impairment. Topical therapies may be inadequate for these patients, necessitating systemic treatment.The objective of EMBRACE was to evaluate the impact on QoL, efficacy and safety of apremilast 30 mg BID in patients with limited skin involvement with plaque psoriasis manifestations in special areas and impaired QoL.EMBRACE (NCT03774875) was a phase 4, randomized, placebo-controlled, multinational study. Patients had plaque psoriasis not controlled by topical therapy; lack of response, contraindication or intolerance to conventional first-line systemic therapy; psoriasis in ≥1 special area (including visible locations, scalp, nails, genital areas or palmoplantar areas); Psoriasis Area and Severity Index (PASI) ≥3 to ≤10; and Dermatology Life Quality Index (DLQI)gt;10. The primary endpoint was DLQI response (≥4-point reduction) at Week 16.Of 277 randomized patients (apremilast: n = 185; placebo: n = 92), 221 completed Week 16 (apremilast: n = 152; placebo: n = 69). The primary endpoint (≥4-point reduction in DLQI at Week 16) was met by significantly more patients receiving apremilast (73.3%) versus placebo (41.3%; p lt; 0.0001). Significantly greater improvement in affected body surface area (BSA) and PASI was observed with apremilast versus placebo at Week 16. There were also significantly greater improvements with apremilast versus placebo in itch numeric rating scale (-2.5 vs. -0.9, p lt; 0.0001) and skin discomfort/pain visual analog scale (-21.5 vs. -5.4, p = 0.0003) and greater achievement of Patient Benefit Index ≥1 (77% vs. 40%, p lt; 0.0001) at Week 16. No new safety signals were observed.Apremilast significantly improved skin-related QoL in patients with limited skin involvement with plaque psoriasis in special areas and highly impaired QoL. The safety profile was consistent with prior apremilast studies.

Background: Biologic treatments have been studied mainly in patients with a long-term history of psoriasis and previous treatment failures. Objectives: The purpose of this primary analysis of the STEPIn study is to determine whether early intervention with secukinumab in patients with new-onset moderate to severe plaque psoriasis is superior to standard of care treatment with narrow band ultraviolet B (nb-UVB) phototherapy. Methods: The STEPIn study is a randomized, open-label, multicentre study to investigate early intervention with 52 weeks of secukinumab 300 mg administered subcutaneously versus standard treatment with nb-UVB phototherapy in patients with new-onset (≤12 months) moderate to severe plaque psoriasis (NCT03020199). The primary and additional secondary endpoints were ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) at Week 52 and Investigator's Global Assessment (IGA mod 2011) 0/1 response at Week 52, respectively. Results: In the secukinumab and nb-UVB study arms, 77/80 and 76/80 randomized patients received at least one dose of study treatment, respectively. The primary endpoint was achieved: 91.1% (70/77) of patients achieved a PASI 90 response at Week 52 in the secukinumab arm versus 42.3% (32/76) in the nb-UVB arm (p < 0.0001, odds ratio [OR] estimate [95% confidence intervals, CI] = 16.3 [5.6, 46.9]). The additional secondary endpoint was also achieved: 85.7% of patients achieved an IGA 0/1 response at Week 52 in the secukinumab arm versus 36.8% in the nb-UVB arm (p < 0.0001). The safety data were consistent with the safety profiles of secukinumab and nb-UVB with no new or unexpected safety signals. Conclusions: Secukinumab was superior to nb-UVB in treating patients with new-onset moderate to severe plaque psoriasis. The high and sustained skin clearance observed indicates that biologic treatment for psoriasis may be more effective if used early in the disease course.

Introduction Patients with plaque psoriasis may experience varying levels of treatment response to different biologics, based on phenotypic characteristics and underlying genetic factors. Nail psoriasis is a common manifestation of psoriasis (approx. 50% of patients) and has been linked to the human leukocyte antigen-C*0602 (HLA-C*0602) allele, which in turn has been associated with differential treatment responses to certain drugs. Here we investigate whether nail involvement in patients with psoriasis can predict differential skin responses to two biologics with different modes of action, namely secukinumab (anti-interleukin-17A) and ustekinumab (anti-interleukin-12/23), to ultimately guide treatment choice. Methods Data were pooled from the CLEAR and CLARITY studies and stratified post hoc by nail involvement status at baseline. Psoriasis Area and Severity Index (PASI) 75 and 90 responses over 52 weeks and absolute PASI ≤ 3, ≤ 1, and 0 values at weeks 16 and 52, were assessed. Results Based on the medical history, 30.4% (269/886) of the patients in the secukinumab arm and 29.7% (265/891) of patients in the ustekinumab arm presented with nail involvement. Nail involvement status had little to no impact on the efficacy of secukinumab, as comparable responses were achieved for patients with and without nail involvement in terms of PASI 75/90, ≤ 3, and 0 responses; slightly lower PASI ≤ 1 reponses were achieved in patients with nail involvement. In the ustekinumab arm, patients with nail involvement achieved lower responses across all endpoints. Conclusions These findings indicate that nail involvement can serve as an observable prognostic factor for efficacy in skin psoriasis treatment and guide the choice between secukinumab and ustekinumab. Trial Registration CLEAR: NCT02074982; CLARITY: NCT02826603.

Introduction In the real-world APPRECIATE study (NCT02740218), most patients with psoriasis demonstrated notable improvements on disease severity measures and reported clinically meaningful treatment benefits with apremilast. Objective We aim to further describe patient-relevant needs and benefits and patient satisfaction with apremilast, including subgroup analyses based on patient characteristics. Methods APPRECIATE, a multinational, retrospective, cross-sectional study, enrolled patients with chronic plaque psoriasis who started apremilast according to the European label. Patient Benefit Index (PBI; range 0 (no patient-relevant benefit) to 4 (maximum patient-relevant benefit), global PBI score ≥ 1 indicating minimum patient-relevant benefit and ≥ 3 indicating high benefit) and nine-item Treatment Satisfaction Questionnaire for Medication (TSQM-9; range 0–100) were assessed 6 (± 1) months after apremilast initiation and summarized descriptively. Relationships between global PBI and TSQM-9 assessments were analyzed by Pearson correlations. Results Of 480 enrolled patients, 347 (72.3%) had remained on apremilast at 6 (± 1) months; 90.9% (300/330) achieved global PBI score ≥ 1. Mean (standard deviation) global PBI score was 2.8 (1.2). Higher achievement of global PBI score ≥ 3 was observed in patients with no prior treatments (61.1% (22/36)) or prior phototherapy (64.6% (42/65)) versus prior conventional systemic (54.4% (100/184)) or biologic (38.6% (17/44)) treatment. Strong correlations were observed between the global PBI score and the TSQM-9 global satisfaction and effectiveness subscale scores. Conclusion Patients continuing apremilast for 6 (± 1) months in APPRECIATE reported patient-relevant treatment benefits. Findings suggest that receiving apremilast earlier versus later in treatment management is consistent with greater improvements in patient-relevant treatment outcomes. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00628-3.

Janus kinase inhibitors (JAKi), such as tofacitinib, baricitinib, upadacitinib or ruxolitinib, are small molecules active on specific intracellular targets and used orally for the treatment of autoimmune or myeloproliferative diseases. Their remarkable therapeutic efficacy is offset by a significant risk of toxicities, essentially dose-dependent and a variable pharmacokinetic profile. The JAKi represent a new therapeutic armamentarium for treating autoimmune, myeloproliferative and inflammatory diseases (incl. COVID-19), but require thorough treatment individualization and close monitoring. Therapeutic Drug Monitoring (TDM) of JAKi could allow a personalized prescription and improve the efficacy-toxicity profile.Les inhibiteurs des Janus kinases (JAKi), tels que le tofacitinib, le baricitinib, l’upadacitinib ou le ruxolitinib, représentent une nouvelle classe de petites molécules actives sur des cibles intra-cellulaires spécifiques, utilisables par voie orale pour traiter des maladies autoimmunes ou néoplasies myéloprolifératives. Leur efficacité thérapeutique remarquable est contrebalancée par un risque significatif de toxicités essentiellement dose-dépendantes et un profil pharmacocinétique variable. Les JAKi constituent une nouvelle arme thérapeutique pour le traitement des maladies autoimmunes, myéloprolifératives et inflammatoires (Covid-19), mais nécessitent une individualisation et un suivi attentifs. Le suivi thérapeutique des médicaments des JAKi pourrait permettre de personnaliser leur prescription et améliorer leur profil efficacité-toxicité.

Summary Background Neutrophilic dermatoses (ND) are a heterogeneous group of diseases, but can often have a relatively similar histological appearance. Aim To identify a combination of biomarkers allowing a better differentiation of ND types. Methods Biopsies were obtained from normal human skin (NS; n = 4), chronic plaque-type psoriasis (PsO; n = 7), paradoxical psoriasis (PP; n = 8), generalized pustular psoriasis (GPP; n = 9), subcorneal pustular dermatosis of Sneddon–Wilkinson (SPD; n = 3), acute generalized exanthematous pustulosis (AGEP; n = 3), hidradenitis suppurativa (HS; n = 7), Sweet syndrome (SS; n = 8) and pyoderma gangrenosum (PG; n = 8). Samples were analysed by immunofluorescence using three biomarkers, interleukin (IL)-17E, inducible nitric oxide synthase (iNOS) and arginase1, each one in combination with two cell markers, myeloperoxidase (MPO) and CD68, which allow the identification of neutrophils and macrophages, respectively. Results We found that SS is characterized by high expression of IL-17E and iNOS in the epidermis, while PG exhibits low expression. The density of the neutrophil infiltrate helps to differentiate PP (high-density infiltrate) from PsO (low-density infiltrate). High expression of arginase1 in the granular layer of the epidermis is a hallmark of SPD. Finally, mature neutrophils and proinflammatory macrophages are readily detectable in PP, SPD and PG, whereas immature neutrophils and anti-inflammatory macrophages are more frequent in GPP, AGEP, HS and SS. Conclusions The analysis of ND by immunofluorescence using IL-17E, iNOS and arginase1 in combination with MPO and CD68 allows for characterization of differential expression patterns in the epidermis as well as the determination of the polarization status of the dermal neutrophils and macrophages. The appropriate markers may help in the differentiation of ND in clinical practice.

Biologics targeting specific cytokines and pathways have revolutionized the management of patients with chronic inflammatory diseases. However, these treatments have their limitations and, surprisingly, can induce novel inflammatory diseases. Here, we present a case of a psoriasis patient developing anti-IL17 induced eczema, an intriguing side effect of IL-17 blockade. The coexistence of psoriasis and eczema in a single patient is uncommon given their distinct and opposing immune mechanisms. Psoriasis is mainly driven by Th17 cells, whereas atopic dermatitis is Th2-dominated. In this article, we propose the yin yang of Th2 and Th17 with IL-4 and IL17 as principal antipodal vectors that control each other. Thus, blocking one of these cytokines can tip the balance between Th2 and Th17 and lead to the induction of the opposing inflammatory pathway via lifting the controlling mediator.Les biologiques ciblant des cytokines spécifiques ont révolutionné la prise en charge des maladies inflammatoires chroniques. Cependant, ces thérapies possèdent leurs propres limites et peuvent – de manière surprenante – induire de nouvelles pathologies inflammatoires. Nous présentons le cas d’un patient psoriasique avec un eczéma induit par anti-IL-17. La coexistence du psoriasis et de l’eczéma atopique chez un même patient est rare, du fait de leurs mécanismes inflammatoires distincts. Le psoriasis est médié par la voie Th17, tandis que l’eczéma atopique est dominé par la voie Th2. Nous proposons un modèle yin-yang entre la voie Th17 et Th2, avec respectivement l’IL-17 et l’IL-4 comme vecteurs opposés. Le blocage de l’une de ces deux cytokines peut perturber cet équilibre dynamique et induire l’expression de la voie inflammatoire opposée par levée du médiateur de contrôle.

Background\ud APPRECIATE is a multinational, observational, retrospective, cross‐sectional study in patients treated for psoriasis with apremilast, an oral phosphodiesterase 4 inhibitor.\ud \ud Objectives\ud To describe the characteristics of patients with psoriasis treated with apremilast in the clinical setting, to evaluate real‐world outcomes of psoriasis treatment with apremilast and to better understand the perspectives of patients and physicians on treatment outcomes.\ud \ud Methods\ud In six European countries, patients with chronic plaque psoriasis treated in clinical practice who could be contacted 6 (±1) months after apremilast initiation were enrolled. Patient characteristics, Dermatology Life Quality Index (DLQI) and Psoriasis Area and Severity Index (PASI) were obtained from medical records when available. Outcomes were evaluated using patient/physician questionnaires.\ud \ud Results\ud In 480 patients at treatment initiation, mean [median; 95% confidence interval (CI)] PASI and DLQI scores were 12.5 (10.7; 11.6–13.4) and 13.4 (13.0; 11.4–14.2), respectively. At 6 (±1) months, 72.3% of patients (n = 347) continued apremilast treatment [discontinuations: lack of efficacy (13.5%), safety (11.7%), other (2.5%)]. In patients continuing treatment, 48.6% achieved a ≥75% reduction in PASI score; mean (95% CI) DLQI score was 5.7 (4.5–6.9), and mean (SD) Patient Benefit Index score was 2.8 (1.2). Physicians perceived clinical improvement in 75.6% of patients. Physicians’ perspective on overall success of apremilast in meeting expectations correlated with patients’ perception of treatment benefit (r = 0.691). Most commonly reported adverse events (>5% of patients) were diarrhoea, nausea and headache.\ud \ud Conclusions\ud Patients in APPRECIATE reported high disease burden despite more moderate skin involvement than those who enrolled in clinical trials of apremilast. Findings from APPRECIATE demonstrate the real‐world value of apremilast for psoriasis treatment, as 7 of 10 patients continued therapy and showed notable improvement in disease severity and quality of life 6 (±1) months after apremilast initiation.

Skin wounds heal by coordinated induction of inflammation and tissue repair, but the initiating events are poorly defined. Here we uncover a fundamental role of commensal skin microbiota in this process and show that it is mediated by the recruitment and the activation of type I interferon (IFN)-producing plasmacytoid DC (pDC). Commensal bacteria colonizing skin wounds trigger activation of neutrophils to express the chemokine CXCL10, which recruits pDC and acts as an antimicrobial protein to kill exposed microbiota, leading to the formation of CXCL10–bacterial DNA complexes. These complexes and not complexes with host-derived DNA activate pDC to produce type I IFNs, which accelerate wound closure by triggering skin inflammation and early T cell–independent wound repair responses, mediated by macrophages and fibroblasts that produce major growth factors required for healing. These findings identify a key function of commensal microbiota in driving a central innate wound healing response of the skin. Gilliet and colleagues demonstrate that skin wound healing occurs through the coordinated action of plasmacytoid dendritic cells, chemokines and skin microbiota.

Introduction Patients with plaque psoriasis often have nail psoriasis, which is difficult to treat. Ixekizumab (IXE) and ustekinumab (UST) are biologics with established efficacy in nail psoriasis. We present post hoc data from a head-to-head trial of IXE and UST (IXORA-S) to examine the efficacy in nail psoriasis in patients with moderate-to-severe plaque psoriasis over 52 weeks. Methods In IXORA-S, randomised patients received IXE (N = 136) or UST (N = 166) per label for 52 weeks. Eighty-four (61.8%) and 105 (63.3%) of the patients treated with IXE or UST, respectively, had baseline fingernail psoriasis (Nail Psoriasis Severity Index [NAPSI] > 0); of these, 54 (64.3%) and 63 (60.0%) patients, respectively, had significant baseline fingernail psoriasis (defined as NAPSI ≥ 16 with ≥ 4 fingernails involved). The proportion of patients achieving NAPSI = 0, a NAPSI score change from baseline and correlations in Psoriasis Area of Severity Index (PASI) and NAPSI improvement over 52 weeks were examined. Results Progressive improvement occurred in both treatment groups over 52 weeks. Statistically significantly more patients achieved NAPSI = 0 with IXE versus UST by week 16–20, and the proportions continued to increase through week 52 among patients with baseline nail psoriasis (61.9 vs. 28.6%, respectively; P

Background Nail psoriasis (NP) is common and of high importance in patients with psoriasis. Complete resolution of NP at week 24-26 is an unambiguous nail outcome accessible for indirect treatment comparison of biologics. Objective To evaluate the comparative efficacy of approved biologics in achieving complete resolution of NP at week 24-26. Methods A network meta-analysis (NMA) was conducted to indirectly compare the efficacy of six biologics in achieving complete resolution of NP at week 24-26 in patients with moderate-to-severe psoriasis and concomitant NP. Complete resolution of NP was defined as a score of zero on the Nail Psoriasis Severity Index (NAPSI), modified NAPSI (mNAPSI) or Physician's Global Assessment of Fingernails (PGA-F). Results The probability of achieving complete resolution of NP was highest for ixekizumab (46.5%; 95% credibility interval [CrI] 35.1-58.0; Surface Under the Cumulative RAnking curve [SUCRA] 97%), followed by brodalumab (37.0%; 17.0-61.0; 79%), adalimumab (28.3%; 24.4-32.4; 62%), guselkumab (27.7%; 21.1-35.1; 58%), ustekinumab (20.8%; 10.2-35.2; 37%), and infliximab (0.8%; 0.0-8.9; 17%). Conclusion In patients with moderate-to-severe psoriasis and concomitant NP, ixekizumab has the greatest likelihood among approved biologics of achieving complete resolution of NP at week 24-26. Findings should be interpreted carefully because of inherent study limitations.

Background: Physician-reported clinical outcome and quality of life (QoL) measures are currently used to assess outcomes and direct treatment of plaque psoriasis. However, people with psoriasis may have different criteria for judging treatment success. Objectives: To build a unified consensus on the definition of ‘freedom from disease’ from a European stakeholder group, including people with psoriasis, dermatologists and nurses. Methods: The modified Delphi consensus methodology was used to define ‘freedom from disease’, with a consensus group consisting of people with psoriasis, nurses and dermatologists. This methodology involved people with psoriasis during the entire process and consisted of a 15-member Facilitating Consensus Panel to drive the programme content and a larger Voting Consensus Panel to vote on defining ‘freedom from disease’. The Facilitating Panel agreed on disease domains, and aspects of each domain were put forward to the Voting Consensus Panel to establish relative importance. Following two voting rounds, a meeting was held to agree on a final consensus statement. Results: The Facilitating Panel consisted of six patient advocacy group representatives, three specialist nurses and six dermatologists. Voting rounds 1 and 2 were completed by 166 and 130 respondents from the Voting Consensus Panel, respectively. The outputs from both rounds of voting were similar, focusing on normality of living, symptom control, and a relationship of mutual respect and trust between the individual with psoriasis and their healthcare professional. The consensus statement emphasizes that ‘freedom from disease’ is multifaceted and includes the following domains ‘management of clinical symptoms’, ‘psychosocial elements’, ‘QoL and well-being’, ‘treatment’ and ‘healthcare team support’. ‘Freedom from disease’ means all aspects are addressed. Conclusions: Freedom from disease in psoriasis is a multicomponent concept including five main domains. This diverse and multifaceted patient perspective will help us to improve understanding of the outcomes of treatment interventions in people with psoriasis.

Background Drug survival, defined as the length of time from initiation to discontinuation of a given therapy, allows comparisons between drugs, helps to predict patient's likelihood of remaining on a specific treatment, and achieving the best decision for each patient in daily clinical practice. Objective The aim of this study was to provide data on drug survival of secukinumab, ixekizumab, brodalumab, guselkumab, tildrakizumab, and risankizumab in a large international cohort, and to identify clinical predictors that might have an impact on the drug survival of these drugs. Methods This was a retrospective, multicentric, multi-country study that provides data of adult patients with moderate to severe psoriasis who started treatment with an interleukin (IL)-17 or IL-23 inhibitor between 1 February 2015 and 31 October 2021. Data were collected from 19 distinct hospital and non-hospital-based dermatology centers from Canada, Czech Republic, Italy, Greece, Portugal, Spain, and Switzerland. Kaplan-Meier estimator and proportional hazard Cox regression models were used for drug survival analysis. Results A total of 4866 treatment courses (4178 patients)-overall time of exposure of 9500 patient-years-were included in this study, with 3164 corresponding to an IL-17 inhibitor (secukinumab, ixekizumab, brodalumab) and 1702 corresponding to an IL-23 inhibitor (guselkumab, risankizumab, tildrakizumab). IL-23 inhibitors had the highest drug survival rates during the entire study period. After 24 months of treatment, the cumulative probabilities of drug survival were 0.92 (95% confidence interval [CI] 0.89-0.95) for risankizumab, 0.90 (95% CI 0.88-0.92) for guselkumab, 0.80 (95% CI 0.76-0.84) for brodalumab, 0.79 (95% CI 0.76-0.82) for ixekizumab, and 0.75 (95% CI 0.73-0.77) for secukinumab. At 36 months, only guselkumab [0.88 (95% CI 0.85-0.91)], ixekizumab [0.73 (95% CI 0.70-0.76)], and secukinumab [0.67 (95% CI 0.65-0.70)] had more than 40 patients at risk of drug discontinuation. Only two drugs had more than 40 patients at risk of drug discontinuation at 48 months, with ixekizumab demonstrating to have a higher cumulative probability of drug survival [0.71 (95% CI 0.68-0.75)] when compared with secukinumab [0.63 (95% CI 0.60-0.66)]. Secondary failure was the main cause for drug discontinuation. According to the final multivariable model, patients receiving risankizumab, guselkumab, and ixekizumab were significantly less likely to discontinue treatment than those receiving secukinumab. Previous exposure to biologic agents, absent family history of psoriasis, higher baseline body mass index (BMI), and higher baseline Psoriasis Area and Severity Index (PASI) were identified as predictors of drug discontinuation. Conclusion The cumulative probability of drug survival of both IL-17 and IL-23 inhibitors was higher than 75% at 24 months, with risankizumab and guselkumab demonstrating to have overall cumulative probabilities >= 90%. Biological agent chosen, prior exposure to biologic agents, higher baseline BMI and PASI values, and absence of family history of psoriasis were identified as predictors for drug discontinuation. Risankizumab, guselkumab, and ixekizumab were less likely to be discontinued than secukinumab.

Papillon-Lefevre Syndrome (PLS) is (OMIM 245'000) a rare genodermatosis, transmitted in an autosomal recessive mode. The disease results from mutations in the CTSC gene (11q14.2) encoding cathepsin C or dipeptidyl peptidase1 . The clinic is marked by recurrent gingivitis, tooth loss and palmoplantar hyperkeratosis. We report the case of a 19-year-old patient who presented with palmoplantar hyperkeratosis and erythemato-squamous plaques (figure 1), with involvement of knees and elbows. The patient had recurrent abscesses mainly on inguinal and axillary areas.

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COVID-19, which is caused by infection with SARS-CoV-2, is characterized by lung pathology and extrapulmonary complications