Changes in Inflammatory Cytokines in Responders and Non-Responders to TNFα Inhibitor and IL-17A Inhibitor: A Study Examining Psoriatic Arthritis Patients.

This study aimed to examine the changes in biomarker levels in responders and non-responders to tumor necrosis factor alpha inhibitor (TNFi) and interleukin-17A inhibitor (IL-17Ai) in psoriatic arthritis (PsA) patients over a 4-month period after treatment initiation. A total of 68 PsA patients initiating either TNFi, IL-17Ai, or methotrexate treatment were included. Blood plasma and clinical outcome measures were collected adjacent to treatment initiation and after four months. A commercially available multiplex immunoassay was included to evaluate 54 biomarkers. Mean changes were used to evaluate change over time. A statistically significant decrease in pro-inflammatory cytokines IL-6 (log-transformed mean change -0.97, 95%CI -4.30; 2.37, [p = 0.032]) and an increase in anti-inflammatory IL-10 (0.38, 95%CI 1.74; 2.50 [p = 0.010]) were seen in TNFi responders. Meanwhile, a statistically significant increase in the target cytokine IL-17A was seen in both IL-17Ai responders (2.49, 95%CI -1.84; 6.85 [p = 0.031]) and non-responders (2.48, 95%CI -1.46; 6.41 [p = 0.001]). This study demonstrated differing changes in cytokine levels when comparing treatment responders and non-responders, highlighting the need to improve the understanding of the different immune response mechanisms explaining different responses to medical treatment in PsA patients.

Risk of major adverse cardiovascular events and all-cause mortality among patients with psoriatic disease treated with tumor necrosis factor-α and interleukin-12/23 inhibitors: a nationwide population-based cohort study in Korea.

PURPOSE: Few studies have investigated the impact of biologics on the risk of major adverse cardiovascular events (MACEs) among Korean patients with psoriatic diseases. We compared the risk of MACEs and all-cause mortality among patients with psoriatic disease treated with tumor necrosis factor (TNF)-α and interleukin (IL)-12/23 inhibitors in Korea. METHODS: Patients with psoriatic disease prescribed with TNF-α and IL-12/23 inhibitors since 2016 were selected from the Korean National Health Insurance Service (NHIS) Database. Follow-up data for MACEs and all-cause mortality between 2016 and 2020 were collected. A total of 2886 individuals were included, including 1987 IL-12/23 inhibitor users and 899 TNF-α inhibitor users. RESULTS: Compared with IL-12/23 inhibitor users, TNF-α inhibitor users had a higher prevalence of dyslipidemia and a significantly higher risk of all-cause mortality but not MACE. After controlling for age, female TNF-α inhibitor users had a significantly increased risk of all-cause mortality. Meanwhile, after controlling for sex, TNF-α inhibitor users aged 60 years or older demonstrated a significantly elevated risk of all-cause mortality. In conclusion, No statistically significant difference in MACE risk was observed between patients who used TNF-α and IL-12/23 inhibitors. Nevertheless, the use of IL-12/23 inhibitors, especially among older and female patients, resulted in a lower overall mortality.

A systematic review of interleukin-31 inhibitors in the treatment of prurigo nodularis.

BACKGROUND: Prurigo nodularis (PN) is a neuroimmunological skin disease. Severe itching is the most challenging symptom which affects patients' quality of life. T helper 2-derived cytokines, such as interleukin-31 and oncostatin M (OSM), play a crucial role in PN pathogenesis. Nemolizumab and vixarelimab are two biologics acting as IL-31 inhibitors. Vixarelimab also suppresses the OSM activity. This systematic review evaluates the efficacy and safety of nemolizumab and vixarelimab in PN management. METHODS: A systematic search was conducted in PubMed/Medline, Ovid Embase, and Web of Science up to September 17th, 2023. Clinical trials and cohort studies published in English were included. RESULTS: Among a total of 96 relevant records, five were included. The results of four studies with 452 patients using nemolizumab showed that a significantly higher percentage of patients treated with nemolizumab demonstrated a reduction in peak pruritus numerical rating scale (PP-NRS) and investigator's global assessment along with improved sleep disturbance (SD) and quality of life than the placebo group. Moreover, one study administered vixarelimab to 49 PN patients, and their finding illustrated a higher rate of subjects who received vixarelimab experienced ≥ 4-point diminution in worst itch NRS, visual analog scale, healing of representative lesions, and SD quality compared to the placebo group. CONCLUSIONS: IL-31 inhibitors suggest distinct advantages in improving pruritus, sleep quality, and overall quality of life in subjects with moderate-to-severe PN. Further clinical studies are recommended to compare the effectiveness of these biologics to other therapeutic choices.

The role of IL-23 and the use of IL-23 inhibitors in psoriatic arthritis.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis characterised by musculoskeletal and extra-articular manifestations, most notably psoriasis. While the underlying pathogenetic mechanisms are not yet fully understood, a central role has been identified for the IL-23/IL-17 pathway. OBJECTIVES: We briefly describe the role of IL-23 in the pathogenesis of PsA and go on to describe the available anti-IL-23 agents and their place in the management of PsA. METHODS: This is a narrative review of the current literature, focussing on the results of the phase 3 studies in PsA for the IL-12/23 p40 inhibitor ustekinumab and the more recent IL-23 p19 inhibitors guselkumab, risankizumab and tildrakizumab. RESULTS: IL-23 triggers expression of IL-17 and other effector cytokines in a variety of cells, leading to tissue inflammation and injury. Targeting IL-23, particularly with p19 inhibitors, appears to be an effective and safe strategy for multiple clinical domains in PsA, most notably the skin, with some differences in efficacy emerging between these agents. CONCLUSION: The development of IL-23 inhibitors represents a significant advance in the management of psoriatic disease. In the absence of head-to-head studies, future data emerging from real-world experiences of individual IL-23 p19 inhibitors will help inform the use of these agents in relation to other biologics in PsA.

Comparison of psoriasis guidelines for use of IL-23 inhibitors in the United States and United Kingdom: a critical appraisal and comprehensive review.

PURPOSE: This review article aims to compare global dermatologic organizations and the clinical practice guidelines available for the use of interleukin (IL)-23 inhibitors in the treatment of psoriasis. MATERIALS AND METHODS: A literature review encompassing systemic therapies for the treatment of psoriasis was conducted. Guidelines from the American Academy of Dermatology (AAD)-National Psoriasis Foundation (NPF), the National Institute for Health and Care Excellence (NICE), and the British Association of Dermatologists (BAD) served as the main comparators in this review. RESULTS: Of the American and European guidelines available for use of IL-23 inhibitors, several organizations are in agreement regarding the dosage and indications of guselkumab, tildrakizumab, and risankizumab. However, there are differences as well as insufficient recommendations concerning laboratory monitoring and screenings as well as contraindications to therapy. CONCLUSION: IL-23 inhibitors are safe and efficacious therapeutic options for patients with psoriasis and should be considered as a potential first-line therapy alone or in combination with topical medications, phototherapy, and other systemic non-biologic agents. Consideration should be given to the evidence-based guidelines of global dermatologic organizations to help guide therapeutic decisions.

Axial spondyloarthritis.

Axial spondyloarthritis (axSpA) encompasses both radiographic and non-radiographic axSpA. It is a chronic inflammatory disease with a predilection for involving the axial skeleton. The most common presenting symptoms are chronic back pain and spinal stiffness but peripheral and extra-musculoskeletal manifestations occur also frequently. The diagnosis of axSpA relies on the recognition of a clinical pattern of the disease, based on clinical, laboratory and imaging features. The Assessment in SpondyloArthritis international Society classification criteria for axSpA are valid and well implemented for research purposes. Sustained disease activity, measured by validated tools such as the Ankylosing Spondylitis Disease Activity Score, leads to irreversible structural damage and poor functioning and therefore should be abrogated. As part of the management algorithm, non-steroidal anti-inflammatory drugs remain as the first line of pharmacological treatment besides physiotherapy. As a second line, tumour necrosis factor inhibitor and interleukin-17 inhibitor are available but recently Janus kinase inhibitors have also shown efficacy in improving symptoms of the disease.

Fibrosis pulmonar inducida por metotrexato en un paciente con psoriasis / Methotrexate-induced pulmonary fibrosis in a patient with psoriasis

La fibrosis pulmonar a causa del metotrexato es un efecto adverso infrecuente, observado principalmente en los pacientes con artritis reumatoide, aunque también se vio, de manera escasa, en el tratamiento de la psoriasis. Se presenta el caso de un paciente con psoriasis que desarrolló fibrosis pulmonar por metotrexato.

Pulmonary fibrosis due to methotrexate is an infrequent adverse event, observed mainly in patients with rheumatoid arthritis, although it has also been poorly described in the treatment of psoriasis. We present the case of a patient with psoriasis who developed pulmonary fibrosis due to methotrexate.

Microbiome characterization and re-design by biologic agents for inflammatory bowel disease insights.

The therapeutic effect of inflammatory bowel disease has improved in the past decades, but most of patients cannot tolerate, do not respond to drugs, or relapse after treating with conventional therapy. Therefore, new and more effective treatment methods are still needed in treatment of IBD. In this review, we will discuss the relevant mechanisms and the latest research progress of biologics (anti-TNF treatments, interleukin inhibitors, integrin inhibitors, antisense oligonucleotide, and JAK inhibitors) for IBD, focus on the efficacy and safety of drugs for moderate-to-severe IBD, and summarize the clinical status and future development direction of biologics in IBD.

Off-label uses of TNF-a inhibitors and IL-12/23 inhibitors in dermatology.

TNF-a inhibitors, which include adalimumab, infliximab, etanercept, certolizumab, and golimumab, and IL-12/23 inhibitor, ustekinumab, have been widely used as a U.S. Food and Drug Administration (FDA) approved for the treatment of psoriasis. Outside of psoriasis, high levels of TNF-a had also been found in several skin diseases including hidradenitis suppurativa. IL-12 and IL-23 play important role in the pathogenesis of SLE, alopecia areata, and vitiligo. This paper reviews the off-label uses of TNF-a inhibitors and IL-12/23 inhibitors in skin disorders.

Guselkumab: the First Selective IL-23 Inhibitor for Active Psoriatic Arthritis in Adults.

INTRODUCTION: Guselkumab is a subcutaneously administered human monoclonal antibody, selectively blocking IL-23 through binding to its p19 subunit. It was initially approved for the treatment of patients with moderate-to-severe plaque-psoriasis who are candidates for systemic therapy or phototherapy. Pubmed and Embase databases were searched for publications, using the following search terms: psoriasis, psoriatic arthritis, guselkumab, risankizumab, tildrakizumab, p19, interleukin 23, guidelines, treatment recommendations, DISCOVER, ECLIPSE, and VOYAGE. AREAS COVERED: Accumulating evidence suggests that the IL-23/Th17 pathway is important in the pathogenesis of both psoriasis and psoriatic arthritis. Following a successful development program in psoriasis, guselkumab was evaluated for its efficacy and safety in psoriatic arthritis in a comprehensive clinical trial program, comprising one phase-2 study and two phase-3 studies (DISCOVER-1 and -2). Complementary data on pharmacokinetics and safety exist from pre-clinical experiments and pooled analyses from two long-term studies in psoriasis (VOYAGE-1 and -2). Based on the DISCOVER-1 and -2 data, guselkumab was approved by the FDA for the treatment of active psoriatic arthritis in 2020. EXPERT OPINION: Guselkumab is the first selective IL-23 inhibitor approved to treat adults with active psoriatic arthritis, broadening therapeutic options in the field through a novel mode of action.

Análise do perfil clínico e epidemiológico de pacientes com artrite psoriásica em ambulatório de reumatologia na Região Amazônica / Clinical and epidemiological profile analysis of patients with psoriatic arthritis in a rheumatology clinic in the Amazon Region

Objetivo: Conhecer o perfil clínico e epidemiológico de pacien- tes portadores de artrite psoriásica de uma região brasileira. Método: Pesquisa observacional, transversal, epidemiológica e documental, baseada na coleta de dados obtidos a partir da análise de 53 prontuários de pacientes cadastrados do Ambu- latório de Reumatologia da Universidade do Estado do Pará, na Região Amazônica. Resultados: Houve predominância do padrão do tipo poliartrite simétrica, sem distinção entre os sexos, com a presença de manifestações extra-articulares, pso- ríase em placas, em uso de metotrexato em doses médias. Con- clusão: Apesar da etiopatogenia da doença ser dependente de fatores genéticos, ambientais e imunológicos e da população amazônica ser muito particular, de uma miscigenação entre eu- ropeus, ameríndios e negros, o perfil clínico e epidemiológicos dos pacientes do Ambulatório de Reumatologia da Universidade do Estado do Pará é semelhante ao das literaturas nacional e internacional.

Objective: To know the clinical and epidemiologic profile of pso- riatic arthritis patients of a Brazilian region. Method: This is an observational, cross-sectional, epidemiological, and documental study, based on the data obtained from the analysis of the medi- cal records of 53 patients registered on the Rheumatology Cli- nic of the Universidade do Estado do Pará, in the Amazon area. Results: There was a predominance of the symmetrical polyar- ticular pattern, with no sexual distinction, extra articular invol- vement, plaque psoriasis, and treatment withn methotrexate, in medium doses. Conclusion: Despite the etiopathogenesis being dependent on genetic, environmental, and immunological fac- tors, and the population of the Amazon being a mix of Europeans, Amerindians, and black people, the clinical and epidemiological profile of the patients of the Rheumatology clinic of the Univer- sidade do Estado do Pará is similar to the ones described on the national and international literature.

Apreciación crítica del estudio "efectividad y seguridad de secukinumab (Cosentyx®) para el tratamiento de psoriasis en placa moderada a severa en adultos" / Critical appraisal of the study "effectiveness and safety of secukinumab (Cosentyx®) for the treatment of moderate to severe plaque psoriasis in adults"

INTRODUCCIÓN: La psoriasis es una enfermedad crónica no transmisible que provoca inflamación de la piel, está mediada inmunológicamente y se caracteriza por presentar un aumento de la proliferación epidérmica. La presentación más frecuente es la psoriasis en placa (psoriasis vulgaris), que se caracteriza por la aparición de parches rojos, engrosados y bien delimitados; a menudo brillantes y cubiertos por escamas plateadas adheridas. Las quejas físicas comunes de esta afección son la irritación cutánea, sensación de ardor, picazón y dolor en las articulaciones. OBJETIVO: Realizar una apreciación crítica del informe de "Efectividad y seguridad de secukinumab (Cosentyx®) para el tratamiento de psoriasis en placa moderada a severa en adultos". METODOLOGÍA: Siguiendo la metodología propuesta por el Instituto de Evaluación Tecnológica en Salud (IETS), inicialmente se realizó una reunión con expertos clínicos y pacientes para exponer los resultados del informe de evaluación de efectividad y seguridad original, a fin de discutir los desenlaces y comparadores utilizados y, eventualmente, identificar en consenso posibles omisiones por parte de los autores de la evaluación. Posteriormente se replicó el protocolo de búsqueda del informe en las diferentes bases de datos de donde se seleccionaron los artículos para el análisis comparado de secukinumab contra adalimumab, etanercept, etanercept + metotrexato, ustekinumab e infliximab, para el tratamiento de psoriasis en placa moderada-grave. El objetivo de esta réplica era actualizar la búsqueda ejecutada por los autores de la evaluación original, a fin de corroborar su correspondencia con los estudios reportados en el informe e identificar posibles omisiones o estudios publicados en fecha posterior al periodo contemplado en la evaluación de efectividad y seguridad, y que aporten evidencia relevante. Finalmente se realizó una discusión amplia de los nuevos estudios identificados, así como de las conclusiones derivadas de la reunión con expertos, a fin de sintetizar la evidencia disponible sobre el tema, considerar las particularidades de la práctica clínica en Colombia y proceder a emitir un concepto sobre la calidad de la evaluación original y sus resultados. RESULTADOS: Los estudios para el tratamiento de psoriasis son escasos y, en general, comparan cada medicamento con placebo. La literatura incluida en la evaluación original es de alta calidad. Sin embargo, no se identificaron estudios que realicen comparaciones directas entre los medicamentos evaluados, de modo que sus resultados deben interpretarse con cautela. Los resultados de la evaluación muestran cierta ventaja en términos de efectividad de secukinumab sobre la mayoría de los otros medicamentos, especialmente para alcanzar PASI75 y PASI90 en la etapa inicial del tratamiento. No obstante, los resultados no son consistentes en el tiempo. Estos resultados no fueron refutados en el proceso de apreciación crítica. La nueva literatura identificada tras la réplica actualizada del protocolo de búsqueda permite llegar a las mismas conclusiones presentadas en el informe de evaluación original, pero es preciso resaltar que en la evaluación no se muestran resultados sobre el perfil de seguridad de secukinumab. De la reunión con expertos clínicos (dermatólogos) y pacientes se determinó que los desenlaces y comparadores utilizados son adecuados y no omiten alternativas relevantes. No obstante, los expertos clínicos refieren que, debido a la reciente inclusión de secukinumab en el mercado mundial, se tiene muy poca experiencia con el manejo de este medicamento en Colombia, aunque los resultados observados en la práctica clínica no muestran una franca ventaja de este medicamento sobre los ya existentes. CONCLUSIONES: Tras la evaluación crítica del documento de evaluación original de efectividad y seguridad se concluyó que la metodología utilizada por los autores es adecuada y que los resultados reportados son consistentes con la literatura clínica disponible. Sin embargo, dada la inexistencia de estudios con comparaciones cabeza a cabeza, se requiere la realización de análisis que comparen en forma directa la efectividad y seguridad de secukinumab con las demás alternativas de tratamiento para el manejo de pacientes adultos con psoriasis en placa moderada a severa. A partir de la apreciación crítica de la evidencia disponible se concluyó que, en la etapa inicial de tratamiento (primeras 4 semanas), secukinumab es levemente más efectivo que sus comparadores para alcanzar PASI75 y PASI90. En opinión de los expertos clínicos esta ventaja puede obedecer a que las aplicaciones de secukinumab son más frecuentes durante este periodo. Sin embargo, esta diferencia se pierde por completo en la etapa de mantenimiento, donde secukinumab tiene una efectividad similar a la de las otras opciones de tratamiento evaluadas. Por lo anterior, se concluye que el tratamiento de la patología de interés en la etapa inicial debería hacerse con secukinumab, pero en la etapa de mantenimiento el tratamiento puede hacerse indistintamente con cualquiera de las alternativas terapéuticas evaluadas.