Corrigendum: The paradigm of IL-23-independent production of IL-17F and IL-17A and their role in chronic inflammatory diseases.

[This corrects the article DOI: 10.3389/fimmu.2023.1191782.].

The paradigm of IL-23-independent production of IL-17F and IL-17A and their role in chronic inflammatory diseases.

Interleukin-17 family (IL-17s) comprises six structurally related members (IL-17A to IL-17F); sequence homology is highest between IL-17A and IL-17F, displaying certain overlapping functions. In general, IL-17A and IL-17F play important roles in chronic inflammation and autoimmunity, controlling bacterial and fungal infections, and signaling mainly through activation of the nuclear factor-kappa B (NF-κB) pathway. The role of IL-17A and IL-17F has been established in chronic immune-mediated inflammatory diseases (IMIDs), such as psoriasis (PsO), psoriatic arthritis (PsA), axial spondylarthritis (axSpA), hidradenitis suppurativa (HS), inflammatory bowel disease (IBD), multiple sclerosis (MS), and asthma. CD4+ helper T cells (Th17) activated by IL-23 are well-studied sources of IL-17A and IL-17F. However, other cellular subtypes can also produce IL-17A and IL-17F, including gamma delta (γδ) T cells, alpha beta (αß) T cells, type 3 innate lymphoid cells (ILC3), natural killer T cells (NKT), or mucosal associated invariant T cells (MAIT). Interestingly, the production of IL-17A and IL-17F by innate and innate-like lymphocytes can take place in an IL-23 independent manner in addition to IL-23 classical pathway. This would explain the limitations of the inhibition of IL-23 in the treatment of patients with certain rheumatic immune-mediated conditions such as axSpA. Despite their coincident functions, IL-17A and IL-17F contribute independently to chronic tissue inflammation having somehow non-redundant roles. Although IL-17A has been more widely studied, both IL-17A and IL-17F are overexpressed in PsO, PsA, axSpA and HS. Therefore, dual inhibition of IL-17A and IL-17F could provide better outcomes than IL-23 or IL-17A blockade.

Recomendaciones de la Sociedad Española de Reumatología sobre el tratamiento y uso de terapias sistémicas biológicas y no biológicas en artritis psoriásica / Recommendations of the Spanish Society of Rheumatology on treatment and use of systemic biological and non-biological therapies in psoriatic arthritis

Objetivo: La primera finalidad de este documento de recomendaciones es proporcionar al clínico la mejor evidencia disponible y, en su defecto, la mejor opinión consensuada por los panelistas para un uso racional y fundado de las diversas opciones de tratamiento con fármacos antirreumáticos modificadores de la enfermedad (FAME) sintéticos y biológicos en artropatía psoriásica (APs). El presente documento también incide sobre aspectos importantes en el manejo de la APs, como el diagnóstico precoz, los objetivos terapéuticos, las comorbilidades y la optimización del tratamiento. Métodos: Las recomendaciones se consensuaron a través de un panel de 8 reumatólogos expertos, previamente seleccionados por la Sociedad Española de Reumatología (SER) mediante una convocatoria abierta. Las fases del trabajo fueron: identificación de las áreas claves para la actualización del consenso anterior, análisis y síntesis de la evidencia científica (sistema modificado de Oxford, CEBM, 2009) y formulación de recomendaciones a partir de esta evidencia y de técnicas de consenso. Resultados: Se emiten un total de 17 recomendaciones para el tratamiento de los pacientes con APs. Seis de ellas de carácter general, que abarcan desde la transcendencia del diagnóstico y tratamiento precoz hasta la importancia de las comorbilidades. El resto, las 11 específicas, se centran en las indicaciones de los FAME y la terapia biológica en las diferentes formas clínicas de la enfermedad. Así mismo, se abordan las situaciones de fracaso a un primer biológico y se incluyen los algoritmos de tratamientos y una tabla con las diferentes terapias biológicas. Conclusiones: Se presenta la actualización de las recomendaciones de la SER para el tratamiento de la APs con FAME y terapia biológica

Objective: The main purpose of this recommendation statement is to provide clinicians with the best available evidence and the best opinion agreed upon by the panelists for a rational use of synthetic disease modifying antirheumatic drugs (DMARDs) and biologicals in psoriatic arthritis (PsA) patients. The present document also focuses on important aspects in the management of PsA, such as early diagnosis, therapeutic objectives, comorbidities and optimization of treatment. Methods: The recommendations were agreed by consensus by a panel of 8 expert rheumatologists, previously selected by the Spanish Society of Rheumatology (SER) through an open call. The phases of the work were: identification of key areas for updating the previous consensus, analysis and synthesis of scientific evidence (modified Oxford system, Centre for Evidence-based Medicine, 2009) and formulation of recommendations based on this evidence and by consensus techniques. Results: Seventeen recommendations were issued for the treatment of PsA patients. Six of them were of general nature, ranging from the early diagnosis and treatment to the importance of assessing comorbidities. The other 11 were focused on the indications for DMARDs and biological therapy in the distinct clinical forms of the disease. Likewise, the situation of failure of the first biological is addressed and treatment algorithms and a table with the different biological therapies are also included. Conclusions: We present the update of SER recommendations for the treatment of PsA with DMARDs and biologics

Recomendaciones sobre el uso de metotrexato en pacientes con artritis psoriásica / Recommendations for the use of methotrexate in psoriatic arthritis

Objetivos: Desarrollar recomendaciones sobre el uso de metotrexato (MTX) en pacientes con artritis psoriásica (APs) basadas en la mejor evidencia y experiencia. Métodos: Se seleccionó un grupo de 12 expertos reumatólogos en el manejo de MTX. Los coordinadores generaron 14 preguntas sobre el uso de MTX en pacientes con APs (perfiles de indicación, eficacia y seguridad) para ser contestadas mediante una revisión sistemática de la literatura. En función de las preguntas se definieron los criterios de inclusión y exclusión y las estrategias de búsqueda (para interrogar Medline, Embase y la Cochrane Library). Dos revisores seleccionaron los artículos resultantes de la búsqueda. Se generaron tablas de evidencia. Paralelamente se evaluaron abstracts de congresos de EULAR y ACR. Con toda esta evidencia los coordinadores generaron 12 recomendaciones preliminares que se evaluaron, discutieron y votaron en una reunión de grupo nominal con el resto de expertos. Para cada recomendación se estableció el nivel de evidencia, grado de recomendación, y grado de acuerdo mediante un Delphi. Se definió acuerdo si al menos el 80% de los participantes contestan sí a la recomendación (sí o no). Resultados: De las 12 recomendaciones preliminares se aceptaron 9 recomendaciones sobre el uso de MTX en la APs. Una se englobó en otra y otras 2 no se llegaron a votar porque se decidió no incluirlas, pero se comentan en el texto final. Conclusiones: Estas recomendaciones pretenden resolver algunos interrogantes clínicos habituales y facilitar la toma de decisiones con el uso de MTX en la APs

Objectives: To develop recommendations for the management of methotrexate (MTX) in psoriatic arthritis (PsA), based on best evidence and experience. Methods: A group of 12 experts on MTX use was selected. The coordinators formulated 14 questions about the use of MTX in PsA patients (indications, efficacy, safety and cost-effectiveness). A systematic review was conducted to answer the questions. Using this information, inclusion and exclusion criteria were established, as were the search strategies (Medline, EMBASE and the Cochrane Library were searched). Two different reviewers selected the articles. Evidence tables were created. At the same time, European League Against Rheumatism and American College of Rheumatology abstracts were evaluated. Based on this evidence, the coordinators proposed 12 preliminary recommendations that the experts discussed and voted on in a nominal group meeting. The level of evidence and grade of recommendation were established using the Oxford Centre for Evidence Based Medicine and the level of agreement with the Delphi technique (2 rounds). Agreement was established if at least 80% of the experts voted yes (yes/no). Results: A total of 12 preliminary recommendations on the use of MTX were proposed, 9 of which were accepted. One was included in a different recommendation and another 2 were not voted on and were thereafter clarified in the main text. Conclusions: These recommendations aim to answer frequent questions and help in decision making strategies when treating PsA patients with MTX

Recommendations of the Spanish Society of Rheumatology on treatment and use of systemic biological and non-biological therapies in psoriatic arthritis. / Recomendaciones de la Sociedad Española de Reumatología sobre el tratamiento y uso de terapias sistémicas biológicas y no biológicas en artritis psoriásica.

OBJECTIVE: The main purpose of this recommendation statement is to provide clinicians with the best available evidence and the best opinion agreed upon by the panelists for a rational use of synthetic disease modifying antirheumatic drugs (DMARDs) and biologicals in psoriatic arthritis (PsA) patients. The present document also focuses on important aspects in the management of PsA, such as early diagnosis, therapeutic objectives, comorbidities and optimization of treatment. METHODS: The recommendations were agreed by consensus by a panel of 8 expert rheumatologists, previously selected by the Spanish Society of Rheumatology (SER) through an open call. The phases of the work were: identification of key areas for updating the previous consensus, analysis and synthesis of scientific evidence (modified Oxford system, Centre for Evidence-based Medicine, 2009) and formulation of recommendations based on this evidence and by consensus techniques. RESULTS: Seventeen recommendations were issued for the treatment of PsA patients. Six of them were of general nature, ranging from the early diagnosis and treatment to the importance of assessing comorbidities. The other 11 were focused on the indications for DMARDs and biological therapy in the distinct clinical forms of the disease. Likewise, the situation of failure of the first biological is addressed and treatment algorithms and a table with the different biological therapies are also included. CONCLUSIONS: We present the update of SER recommendations for the treatment of PsA with DMARDs and biologics.

The TNFRSF1B rs1061622 polymorphism (p.M196R) is associated with biological drug outcome in Psoriasis patients.

Genetic factors are involved not only in the overall risk of suffering psoriasis, but also in their clinical characteristics and eventually in drug outcome. Biological therapies have dramatically improved the prognosis of Psoriasis. However, these treatments are very expensive and patients often exhibit a heterogeneous response that could be partially attributed to their genetic background. Thus, the research for genetic markers in psoriatic patients that could predict a poor response to biological therapies is an important issue. Our aim was to evaluate the effect of DNA variants at the "TNFα pathway" that could affect the risk of developing Psoriasis or the response to biological therapies among these patients. The genetic association study included a total of 518 Psoriatic patients and 480 healthy controls. Ninety of these patients received biological treatment and based on the change in the PASI score after 24 weeks were classified as good (PASI score ≥75%), intermediate (PASI 50-75), and non-responders (PASI <50). Next generation sequencing (NGS) with semiconductor-array technology was used to identify the nucleotide variants in the TNF α, TNFRSF1A and TNFRSF1B, and we only found three missense amino acid changes, all in TNFRSF1B. Interestingly, we found a significantly higher frequency of rs1061622 G carriers among CW6-positive patients (p = 0.004; OR = 1.69, 95% CI = 1.18-2.41). Allele G (p.196R) carriers were significantly more frequent in the non-responder group (56%) (p = 0.05). In conclusion, we report a significant association between the TNFRSF1B p.M196R variant and the risk for psoriasis and the response to treatment with anti-TNF or anti-Il-12/Il-23. The genotyping of this polymorphism could help to optimize the treatment by identifying patients with a likely poor response to biological drugs.

Consenso SER sobre la gestión de riesgo del tratamiento con terapias biológicas en pacientes con enfermedades reumáticas / Consensus statement of the spanish society of rheumatology on risk management of biologic therapy in rheumatic patients

Objetivo: Dado el creciente uso de las terapias biológicas en distintas enfermedades reumatológicas, y la importancia de la gestión de riesgo de las mismas, desde la Sociedad Española de Reumatología (SER) se ha impulsado el desarrollo de recomendaciones basadas en la mejor evidencia posible. Estas deben de servir de referencia para reumatólogos e implicados en el tratamiento de pacientes en tratamiento o en los que se quiere indicar la terapia biológica independientemente de su enfermedad de base. Métodos: Las recomendaciones se emitieron siguiendo la metodología de grupos nominales. El nivel de evidencia y el grado de recomendación se clasificaron según el modelo del Center for Evidence Based Medicine de Oxford y el grado de acuerdo se extrajo por técnica Delphi. Se utilizó toda la información de consensos y guías de práctica clínica previas. Resultados: Se realizan recomendaciones sobre la gestión del riesgo del uso de las terapias biológicas en pacientes con enfermedades reumática. Incluyen la gestión del riesgo de la indicación, gestión del riesgo antes de iniciar el tratamiento, gestión del riesgo durante el seguimiento, actitud ante acontecimientos adversos, y actitud en situaciones especiales. Conclusiones: Se presentan las recomendaciones SER sobre la gestión del riesgo del tratamiento con terapias biológicas (AU)

Objective: Due to the increasing use of biologic therapy in rheumatic diseases and the importance of its risk management, the Spanish Society of Rheumatology (SER) has promoted the development of recommendations based on the best evidence available. These recommendations should be a reference to rheumatologists and those involved in the treatment of patients who are using, or about to use biologic therapy irrespectively of the rheumatic disease. Methods: Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and degree of recommendation were classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through a Delphi technique. Evidence from previous consensus and clinical guidelines was used. Results: We have produced recommendations on risk management of biologic therapy in rheumatic patients. These recommendations include indication risk management, risk management before the use of biologic therapy, risk management during follow-up, attitude to adverse events, and attitude to special situations. Conclusions: We present the SER recommendations related to biologic therapy risk management (AU)

[Consensus statement of the Spanish Society of Rheumatology on risk management of biologic therapy in rheumatic patients]. / Consenso SER sobre la gestión de riesgo del tratamiento con terapias biológicas en pacientes con enfermedades reumáticas.

OBJECTIVE: Due to the increasing use of biologic therapy in rheumatic diseases and the importance of its risk management, the Spanish Society of Rheumatology (SER) has promoted the development of recommendations based on the best evidence available. These recommendations should be a reference to rheumatologists and those involved in the treatment of patients who are using, or about to use biologic therapy irrespectively of the rheumatic disease. METHODS: Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and degree of recommendation were classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through a Delphi technique. Evidence from previous consensus and clinical guidelines was used. RESULTS: We have produced recommendations on risk management of biologic therapy in rheumatic patients. These recommendations include indication risk management, risk management before the use of biologic therapy, risk management during follow-up, attitude to adverse events, and attitude to special situations. CONCLUSIONS: We present the SER recommendations related to biologic therapy risk management.