Secukinumab long-term efficacy and safety in psoriasis through to year 5 of treatment: results of a randomized extension of the phase III ERASURE and FIXTURE trials.

BACKGROUND: In the long-term extension study of the ERASURE and FIXTURE trials, the efficacy of secukinumab (a fully human anti-interleukin-17A monoclonal antibody) was demonstrated to have been maintained through to year 3 of treatment in moderate-to-severe plaque psoriasis. OBJECTIVES: To assess the efficacy and safety of secukinumab through to year 5 of treatment in moderate-to-severe plaque psoriasis. METHODS: Responders with ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) from two core trials - ERASURE and FIXTURE - were randomized 2 : 1 at year 1 (end of core trials) to either the same dose (300 or 150 mg, continuous treatment) or placebo (treatment withdrawal) every 4 weeks, until year 3 or relapse (> 50% reduction in maximal PASI from core study baseline). Partial responders (achieving PASI 50 but not PASI 75) at year 1 continued at the same dose as in the core trials. At year 3, all patients received open-label secukinumab treatment, with those on secukinumab 300 mg continuing on their dose, while those on secukinumab 150 mg or placebo received secukinumab 150 or 300 mg based on the physician's discretion. The study is registered on ClinicalTrials.gov with the identifier NCT01544595. RESULTS: Most patients randomized to placebo at year 1 relapsed, but the response was rapidly recaptured upon reinitiation of treatment. PASI responses were sustained with secukinumab through to year 5. The PASI responses for the 300 mg responders + partial responders group at year 1 (PASI 75/90/100: 86.8%/72.8%/45.9%) trended downwards until year 3 (PASI 75/90/100: 82.3%/58.4%/32.7%) and then remained stable through year 4 (PASI 75/90/100: 83.3%/60.1%/32.2%) until year 5 (PASI 75/90/100: 81.1%/62.8%/35.1%). Dermatology Life Quality Index showed sustained benefit up to year 5. Absolute PASI responses were maintained throughout the study. The most common adverse events (AEs) were infections and infestations, nasopharyngitis, and upper respiratory tract infections (URTIs). The overall exposure-adjusted incidence rate (EAIR; with 95% confidence interval) for all AEs was 139.9 (130.3-149.9). EAIRs for Crohn's disease and neutropenia were 0.1 (0.0-0.3) and 0.5 (0.3-0.8), respectively. CONCLUSIONS: The 4-year extension of two pivotal phase III trials demonstrated that secukinumab treatment was effective through to year 5 and improved quality of life in patients with moderate-to-severe plaque psoriasis. The most common AEs were infections and infestations, nasopharyngitis, and URTIs. The safety profile was consistent with that in the secukinumab phase II/III clinical development programme.

Sustained Effectiveness of Secukinumab Across Different Body Regions in Patients with Moderate-to-Severe Plaque Psoriasis from the PURE Registry.

INTRODUCTION: The association between physician-reported and patient-reported outcomes in patients with psoriasis is not adequately explored. Trends in PASI scores across body regions and the descriptive correspondence between physician-reported PASI components and patient-reported Psoriasis Symptom Diary are reported here. METHODS: PURE is a prospective observational study in adult patients from Canada and Latin America with moderate-to-severe chronic plaque psoriasis. The study enrolled 2362 adult patients treated with secukinumab versus other approved therapies (1:1 ratio). The PASI total score, PASI sub-scores for erythema, thickening, and scaling, and PASI scores for each body region were evaluated and further correlated with disease impact using the Psoriasis Symptom Diary. RESULTS: Secukinumab treatment showed early reduction in the PASI total score (mean ± SD) from 13.3 ± 9.02 at baseline to 2.3 ± 3.99 at 3 months; a similar trend was observed for PASI sub-scores for erythema (4.8 ± 3.21 to 0.9 ± 1.44), thickening (4.3 ± 3.00 to 0.7 ± 1.33) and scaling (4.2 ± 3.04 to 0.7 ± 1.30). The reduction in PASI total and sub-scores were sustained up to 36 months. Psoriasis Symptom Diary component scores related to redness, cracking, and scaling showed a similar reduction from baseline at 3 months that was also sustained up to 36 months. PASI regional scores for each body region showed reduction at 3 months with disease in the lower limbs being more treatment resistant. Safety profile of secukinumab was consistent with its established safety profile without any new or unexpected signals. CONCLUSIONS: Overall, an early and sustained resolution of erythema, thickening, and scaling was observed. Improvements were evident across all body regions, with the most persistent disease seen in the lower limbs. Trends in disease severity, as assessed by physicians using PASI, broadly reflected the trend in the comparable questions of the Psoriasis Symptom Diary assessed by patients.

Effectiveness and Safety of Secukinumab in Latin American Patients with Moderate to Severe Plaque Psoriasis: PURE Registry 12-Month Data.

BACKGROUND:  The efficacy and safety of secukinumab in patients with psoriasis has been established in randomised clinical trials. However, data on effectiveness and safety of secukinumab in Latin American real-world settings are scarce. OBJECTIVES: To evaluate the effectiveness and safety of secukinumab in real-world settings in patients with psoriasis in Latin America. METHODS: PURE is an ongoing multinational, prospective, observational study in patients with moderate-to-severe chronic plaque psoriasis in Canada and Latin America assessing the real-world safety and effectiveness of secukinumab and other approved therapies. The study enrolled (1:1) patients treated with secukinumab versus other approved therapies (other Tx) per local standard of care from 81 community- and hospital-based speciality sites (21 in Latin America). Here, we report effectiveness and safety outcomes with secukinumab and other Tx for plaque psoriasis for up to 12 months in a Latin American population. RESULTS: Overall, 187 patients were included in the analysis, 89 of whom initiated secukinumab treatment and 98 of whom received other Tx. At month 12, 84.4%, 71.1% and 53.3% of patients treated with secukinumab achieved Psoriasis Area and Severity Index (PASI) 75/90/100, respectively, compared with 66.7%, 47.9% and 29.2% of patients who received other Tx. Investigator Global Assessment (IGA) 0/1 responders in secukinumab versus other Tx were 78.3% versus 36.7% at month 3 and 81.8% versus 66.7% at month 12, respectively. Overall, the proportion of patients achieving Dermatology Life Quality Index (DLQI) 0/1 improved from 6.9% at baseline to 76.5% at month 12 in patients treated with secukinumab versus 5.6% at baseline to 54.5% at month 12 in patients on other Tx. No unexpected adverse events were reported during the 12-month observation period. CONCLUSION: Secukinumab demonstrated real-world effectiveness and improved dermatology quality-of-life in chronic plaque psoriasis patients from Latin America. TRIAL REGISTRATION: PURE: NCT02786186.

Metagenomic analysis of gut microbiota in non-treated plaque psoriasis patients stratified by disease severity: development of a new Psoriasis-Microbiome Index.

Psoriasis is an immune-mediated skin disorder. Imbalance of gut microbial populations has been implicated in many diseases. We aimed to investigate whether there were differences in gut microbiota in psoriasis patients vs non-psoriasis controls and between psoriasis severity groups. 55 psoriasis patients and 27 controls were included. V3-V4 regions of the 16S rRNA gene of fecal samples were analyzed using Illumina MiSeq. Bioinformatic analysis was performed. We found changes in gut microbiome composition depending on their psoriasis status as determined by weighted unifrac (p < 0.05), in particular an increase in Firmicutes and depletion of Bacteroidetes in psoriasis patients. Additionally, the Faecalibacterium and Blautia genus were higher in psoriasis patients while Bacteroides and Paraprevotella in non-psoriasis controls (p < 0.05, LDA score > 2). Moderate-to-severe psoriasis patients had lower biodiversity than mild psoriatic patients (p = 0.049). No differences for beta-diversity were found. We developed a Psoriasis-Microbiota Index (PMI), which discriminated among psoriasis patients and controls with sensitivity: 0.78 and specificity: 0.79. Furthermore, we performed a meta-analysis with published data to validate this index. We demonstrated gut dysbiosis in psoriasis patients, suggesting a role in psoriasis pathophysiology. Furthermore, we developed a PMI with the potential to discriminate between psoriasis patients and controls across different populations, which could be used as a biomarker in the clinical practice.

Rationale, objectives and design of PURE, a prospective registry of patients with moderate to severe chronic plaque psoriasis in Canada and Latin America.

BACKGROUND: Treatment options for the management of moderate to severe plaque psoriasis include phototherapy, oral systemic agents, and biologic therapy. Secukinumab, a fully human monoclonal antibody that selectively targets IL-17A, is the first IL-17 antagonist approved for this patient population. Long-term observational data are required for establishing the true population-based benefit-risk ratio of approved treatments. PURE is a multinational registry that will assess the real-world safety and effectiveness of secukinumab and other approved therapies in the management of patients with moderate to severe psoriasis. METHODS: This is a multinational (Canadian and Latin American), prospective, observational study of adult patients with moderate to severe psoriasis that initiate treatment with secukinumab or other approved therapies as per local standard of care. A total of 2500 patients (1250 per cohort) will be recruited in the practices of hospital and community dermatologists. Decision regarding treatment must have been reached prior to and independent of patient enrollment in the study. The study includes a 5-year follow-up with recommended assessments at Baseline, 3 and 6 months post-Baseline, and every 6 months thereafter. The primary objective of the study is safety. Secondary outcome measures relate to effectiveness (Investigator's Global Assessment -IGA mod 2011-, Psoriasis Areas and Severity Index, Body Surface Area), patient reported outcomes (Dermatology Life Quality Index, Work Productivity and Activity Impairment Questionnaire, Hospital Anxiety and Depression Scale, Psoriasis Epidemiology Screening Tool, Psoriasis Symptom Diary, and Treatment Satisfaction Questionnaire), and healthcare resource utilization. DISCUSSION: This is the first observational study in Canada and Latin America assessing the real-world safety and effectiveness of secukinumab in the management of moderate to severe psoriasis. The extensive clinical, patient-reported and health economic outcomes collected will allow the comprehensive evaluation of this new treatment in comparison to other approved therapies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02786186 ; date of registration: May 30, 2016.

Infectious skin disorders encountered in a pediatric emergency department of a tertiary care hospital in Argentina: a descriptive study.

BACKGROUND: Infectious skin disorders (ISDs) are commonly seen in pediatric emergency departments (PED), however the exact frequency is unknown. We provide an accurate evaluation of the incidence and characteristics of ISDs diagnosed in a PED from Buenos Aires, Argentina, over a 1-year period. METHODS: Prospectively, descriptive study of children evaluated in the PED with ISDs during 2016. ISDs were analyzed on the basis of their incidence, patient demographics, seasonal variations, and hospitalization rates. RESULTS: ISDs were diagnosed in 1680 (67.9%) of the skin consultations (M/F: 1.1; mean age: 4.4 ± 3.7 years). Bacterial infections were observed in 932 (55.5%) cases. Viral infections were seen in 604 patients (35.9%). Fungal and parasite skin infections were diagnosed in 33 (2%) and 111 (6.6%) children, respectively. The most frequent ISDs according to the etiology group were impetigo 377 (22.4%), varicella 397 (23.6%), tinea capitis 10 (0.6%), and scabies 109 (6.5%). A higher frequency of ISDs were reported during the summer (38.4%) and spring (38.2%) months. Bacterial skin infections were more frequent during the summer months, while viral skin infections were more prevalent during spring. Parasitic skin infections were diagnosed more frequently during the winter months. No differences were seen for mycotic skin infections. Hospitalization rate was 1% (all for bacterial skin infections). CONCLUSION: Our data reveal the extremely high frequency of ISDs seen at the PED, underlying the need for closer cooperation between dermatologists and pediatricians.

Secukinumab is Efficacious and Safe in Hispanic Patients with Moderate-to-Severe Plaque Psoriasis: Pooled Analysis of Four Phase 3 Trials.

INTRODUCTION: There is little evidence available on the efficacy and safety of biologic therapies for the treatment of psoriasis in Hispanic patients. Secukinumab is demonstrated to be highly effective for clearing psoriasis. The aim of this study was to compare the efficacy and safety of secukinumab in Hispanic and non-Hispanic patients. METHODS: Data were pooled from four phase 3 studies of secukinumab in patients with moderate-to-severe plaque psoriasis. Patients who self-identified as Hispanic were included in the Hispanic subgroup. RESULTS: Efficacy responses (Psoriasis Area and Severity Index [PASI] 75/90/100 and Investigator's Global Assessment 2011 modified version 0/1) for secukinumab 300 mg were greater than for etanercept at week 12 in the Hispanic and non-Hispanic patient subgroups. At week 12 with secukinumab 300 mg, PASI 90/100 responses were achieved by 70.6%/35.9% of Hispanic patients and 58.0%/28.1% of non-Hispanic patients. At week 12 with secukinumab 150 mg, PASI 90/100 responses were achieved by 59.5%/25.1% of Hispanic patients and 41.2%/13.4% of non-Hispanic patients. In both subgroups, peak efficacy responses with secukinumab were observed at week 16 and were maintained to week 52. CONCLUSIONS: Secukinumab is highly effective for clearing psoriasis in both Hispanic and non-Hispanic patients. FUNDING: Novartis Pharmaceutical Corporation.

Exantema periflexural asimétrico de la infancia, dos formas de presentación / Asymmetric periflexural exanthem of childhood, two forms of presentation

El exantema periflexural asimétrico de la infancia es una entidad benigna, autolimitada, subdiagnosticada, de etiología desconocida, que compromete mayormente niñas de edad preescolar. Tiene predominancia estacional (invierno y primavera). Su diagnóstico es clínico, y se presenta como un exantema escarlatiniforme, morbiliforme o eccematoso, que generalmente comienza en la axila y se extiende centrífugamente hacia el tronco y el miembro superior homolateral. Puede acompañarse de adenopatías regionales y fiebre. No requiere tratamiento específico, salvo el uso de cremas humectantes y antihistamínicos, en caso de presentar prurito. Se describen 2 pacientes con diferentes formas de presentación de esta entidad, una típica y otra infrecuente.

Asymmetric periflexural exanthema of childhood is a benign, self-limited, underdiagnosed disease of unknown etiology that mainly affects girls at preschool age. It has seasonal predominance (winter and spring). The diagnosis is clinical and is presented as scarlatinform, morbiliform or eczematous exanthem that generally begins in the axilla and centrifugally extends to the trunk and the homolateral upper limb. It may be accompanied with regional adenopathies and fever. It does not require specific treatment except for the use of moisturizing and antihistaminic creams in case of pruritus. Two patients with different forms of presentation, one typical and another unfrequent, were described.

Dermatitis atópica en niños: estudio comparativo en dos grupos etarios / Atopic dermatitis in children: a comparative survey among 2 age groups

Introduction: Prevalence of atopic dermatitis (AD) has increased steadily. Risk factors are being researched worldwide. There is little data available in Agentina. Objectives y Methods: This study included 722 children > 12 and < 60 months of age residing in an urban community in Buenos Aires. UK's Working Party's criteria were used to establish the prevalence of AD. The objectives were a) to establish the prevalence of in children < 36 and > 36 months of age, b) evaluate gender differences in prevalence, and c) evaluate association between AD and the following variables: family history of atopia and degree of consanguinity; number of people living together < 4; use of synthetic clothing in direct contact with the skin; tobacco use within the home; use of rugs/carpeting within the home; environmental contaminating factors in each age group. χ2 was used to calculate associations in a logistic regression model. Results: Prevalence of AD was 31,3 percent (CI: 27,235,6) among children < 36 months and 49,6 percent (CI: 43,1-56,1) among children > 36 months. AD was more prevalent among younger males. Family history of atopia, use of synthetic material, and living near a factory were associated to AD in both age groups. Using rugs/carpeting inside the house was associated to the disease only in younger children. Conclusion: Ain elevated prevalence of ALD was found in this low-income population. It predominates among older children, which differs from commonly accepted findings. Not all evaluated risk factors were associated to the disease.

Introducción: La prevalencia de la dermatitis atópica (DA) ha aumentado sostenidamente y sus factores de riesgo son investigados mundialmente. En la Agentina, sin embargo, existen escasos datos disponibles. Objetivos y Métodos: Estudio de prevalencia, de corte transversal que incluyó 722 niños > 12 y < 60 meses de edad pertenecientes a una comunidad urbana bonaerense. Se utilizaron los criterios del the U.K. Working Party's para definir DA. Los objetivos fueron establecer la prevalencia de la DA en niños < 36 meses y > 36 meses de edad, conocer si existen diferencias de prevalencia según sexo, y evaluar asociaciones entre DA y las siguientes variables: presencia de antecedentes familiares de atopía según grado, número de convivientes < 4, uso de ropa sintética en contacto directo con la piel, consumo de tabaco en el interior de la vivienda, alfombra/s dentro del hogar y factores contaminantes medioambientales en cada grupo etario. Se utilizó la prueba de χ² para calcular asociaciones, que de ser significativas se incluyeron en un modelo de regresión logística. Resultados: La prevalencia de DA fue del 31,3 por ciento (IC: 27,2-35,6) en los < 36 meses y 49,6 por ciento (IC: 43,1-56,1) en los > 36 meses. La DA prevaleció en el sexo masculino en los niños más pequeños. El AAF de atopía, el uso de ropa de material sintético y habitar cerca de una fábrica se relacionaron con la DA en ambos grupos etarios, en tanto poseer alfombra/s dentro del hogar se asoció con la enfermedad sólo en los niños pequeños. Conclusión: Hallamos una elevada prevalencia de DA en esta población de bajos recursos, y que la DA predominó en niños mayores, resultados que se contraponen a lo actualmente aceptado, y que no todos los factores de riesgo investigados se asociaron con la enfermedad.

Terapias alternativas en psoriasis / Alternative therapies in psoriasis

La psoriasis, como muchas de las enfermedades crónicas, resulta un campo propicio para las TA, existiendo estudios que reportan su utilización por más del 50% de los pacientes encuestados. Con el fin de ahondar sobre las TA disponibles, su eficacia, seguridad y motivaciones para su uso o rechazo en los pacientes con psoriasis, se divide esta comunicación en diferentes secciones que incluyen: la definición de TA, ciertas consideraciones históricas, el concepto del placebo y su relación con las TA, las TA disponibles para los pacientes con psoriasis tanto en la literatura médica como en internet, las motivaciones para su utilización por parte de los pacientes y la visión que tienen los médicos sobre las mismas.

Púrpura localizada: manifestación cutánea de amiloidosis sistémica primaria / Localized purpura: cutaneous manifestation of primary cutaneous amyloidosis

Presentamos el caso de un paciente con amiloidosis sistémica primaria que presentaba las manifestaciones cutáneas características. El paciente tenía lesiones purpúricas en región periorbitaria y tronco. En este caso se asoció a una paraproteinemia no mieloma. Destacamos la importancia de las lesiones cutáneas en el diagnóstico de la amiloidosis sistémica primaria dado que son fáciles de reconocer. Además, su presencia permite sospechar la amiloidosis sistémica, la cual se puede confirmar mediante la biopsia cutánea de dichas lesiones

Púrpura localizada: manifestación cutánea de amiloidosis sistémica primaria / Localized purpura: cutaneous manifestation of primary cutaneous amyloidosis

Presentamos el caso de un paciente con amiloidosis sistémica primaria que presentaba las manifestaciones cutáneas características. El paciente tenía lesiones purpúricas en región periorbitaria y tronco. En este caso se asoció a una paraproteinemia no mieloma. Destacamos la importancia de las lesiones cutáneas en el diagnóstico de la amiloidosis sistémica primaria dado que son fáciles de reconocer. Además, su presencia permite sospechar la amiloidosis sistémica, la cual se puede confirmar mediante la biopsia cutánea de dichas lesiones (AU)

Esclerosis tuberosa: a propósito de un caso con compromiso multisistémico y evolución fatal / Tuberous sclerosis: case report with multisystemic involvement and fatal outcome

Presentamos una paciente de 45 años, con lesiones cutaneas características de esclerosis tuberosa: maculas hipopigmentadas en el tronco, angiofibromas solitarios en la cara, un angiofibroma en placa en la frente y un nevo conectivo en la espalda. También presenta compromiso neurológico: epilepsia, calcificaciones periventriculares y nódulos subependimarios sin déficit cognitivo, compromiso pulmonar: linfangiomiomatosis, alteraciones oftalmológicas: hamartomas retinianos, y manifestaciones renales: angiomiolipomas y quistes renales múltiples. Destacamos el importante compromiso multisistémico de este caso y la rareza de la linfangiomiomatosis, motivo por el cual el pronóstico de la enfermedad empeora. A pesar de ello, y en contra de lo esperado, la paciente sobrevive hasta los 45 años y finalmente fallece por complicaciones propias de su patología de base

Esclerosis tuberosa: a propósito de un caso con compromiso multisistémico y evolución fatal / Tuberous sclerosis: case report with multisystemic involvement and fatal outcome

Presentamos una paciente de 45 años, con lesiones cutaneas características de esclerosis tuberosa: maculas hipopigmentadas en el tronco, angiofibromas solitarios en la cara, un angiofibroma en placa en la frente y un nevo conectivo en la espalda. También presenta compromiso neurológico: epilepsia, calcificaciones periventriculares y nódulos subependimarios sin déficit cognitivo, compromiso pulmonar: linfangiomiomatosis, alteraciones oftalmológicas: hamartomas retinianos, y manifestaciones renales: angiomiolipomas y quistes renales múltiples. Destacamos el importante compromiso multisistémico de este caso y la rareza de la linfangiomiomatosis, motivo por el cual el pronóstico de la enfermedad empeora. A pesar de ello, y en contra de lo esperado, la paciente sobrevive hasta los 45 años y finalmente fallece por complicaciones propias de su patología de base (AU)

Cutaneous true histiocytic malignancy: true histiocytic lymphoma.

True histiocytic malignancies (THM) are controversial disorders that are being re-evaluated with modern cellular and molecular biology techniques. True histiocytic lymphoma (THL) is a low-incidence, poor-prognosis THM. It mainly affects the skin, gastrointestinal tract, and bone tissues. Occasionally, skin lesions are the presenting clinical features. A patient with initially cutaneous THL is described. This and other reported cases confirm that THM are a nosologic entity by themselves.