Disease control in patients with ankylosing spondylitis in real clinical practice in Spain: Results of the MIDAS study.

INTRODUCTION AND OBJECTIVES: Understanding the disease activity is fundamental to improve patient prognosis and patients' quality of life. MiDAS study described disease activity in ankylosing spondylitis (AS) Spanish patients and the proportion of them with controlled disease. METHODS: Observational, cross-sectional, multicenter study carried out under conditions of routine clinical practice. Adult (≥18 years) patients with ≥6 months since AS diagnosis treated ≥3 months prior to inclusion. The primary endpoint was the percentage of patients with low disease activity assessed through BASDAI (primary endpoint) and ASDAS-CRP (secondary endpoint). RESULTS: 313 AS patients included: 75.7% male; 78.5% HLA-B*27 positive; mean (SD) baseline age of 50.4 (12.0) years; mean (SD) disease duration of 15.5 (11.6) years; 73.5% were treated with biological disease-modifying antirheumatic drugs (DMARDs), 22.4% with non-biological DMARDs and 53.7% with non-steroidal anti-inflammatory drugs, alone or in combination. Monotherapy with biologics and non-biologics was used by 29.7% and 26.8% of patients, respectively. According to BASDAI, 38.0% were in remission (BASDAI≤2) and 64.5% showed adequate disease control (BASDAI<4). According to ASDAS-CRP, 29.4% achieved remission (ASDAS-CRP<1.3) and 28.1% low disease activity (1.3≤ASDAS-CRP<2.1). CONCLUSIONS: Almost two thirds of the AS patients recruited had low disease activity, with about one third of them being in remission (BASDAI≤2, ASDAS-CRP<1.3). These results highlight the existing room for improvement in treating AS patients in clinical practice.

Disease control in patients with psoriatic arthritis in real clinical practice in Spain: MiDAS study.

OBJECTIVE: MiDAS study assessed the percentage of psoriatic arthritis (PsA) patients treated in routine clinical practice who achieved control of disease activity according to Disease Activity in Psoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA). METHODS: Observational, non-interventional, cross-sectional, multicenter study conducted under conditions of routine clinical practice in 36 centers with outpatient rheumatology clinics in Spanish public hospitals. Patients included were adults (≥18 years) with ≥6 months PsA diagnosis according to classification for PsA (CASPAR) criteria and undergoing treatment ≥3 months. The main variable evaluated was the percentage of patients under remission and low disease activity, assessed through DAPSA and MDA. RESULTS: 313 patients with PsA were included: 54.3% male; with mean age of 54.1±12.2 years and mean disease duration of 10.5±9.0 years. Mean C-reactive protein (CRP) serum levels were 4.9±7.3mg/L. At the study visit, 58.5% of patients were in monotherapy (17.6% biological and 40.9% non-biological) and 41.2% were receiving biological and non-biological therapy. 59.4% of patients showed low disease activity (DAPSA≤14) and 19.8% were on remission (DAPSA≤4). Moreover, 51.4% of the patients reached an MDA status (≥5 MDA). CONCLUSIONS: Around 40% of PsA patients presented uncontrolled disease, highlighting the need to improve the management of these patients in clinical practice.

Using natural language processing to explore characteristics and management of patients with axial spondyloarthritis and psoriatic arthritis treated under real-world conditions in Spain: SpAINET study.

Background: Spondyloarthritis (SpA) is a group of related but phenotypically distinct inflammatory disorders that include axial SpA (axSpA) and psoriatic arthritis (PsA). Information on the characteristics and management of these patients in the real world remains scarce. Objectives: To explore the characteristics and management [disease activity assessment and treatment with secukinumab (SEC) or other biologic disease-modifying antirheumatic drugs (bDMARDs)] of axSpA and PsA patients using natural language processing (NLP) in Electronic Health Records (EHRs). Design: National, multicenter, observational, and retrospective study. Methods: We analyzed free-text and structured clinical information from EHR at three hospitals. All adult patients with axSpA, PsA or non-classified SpA from 2018 to 2021 with minimum follow-up of three months were included when starting SEC or other bDMARDs. Clinical variables were extracted using EHRead® technology based on Systemized Nomenclature of Medicine-Clinical Terms (SNOMED CT) terminology. Results: Out of 887,735 patients, 758 were included, of which 328 had axSpA [58.5% male; mean (SD) age of 50.7 (12.7) years], 365 PsA [54.8% female, 53.9 (12.4) years], and 65 non-classified SpA. Mean (SD) time since diagnosis was 36.8 (61.0) and 24.1 (35.2) months for axSpA and PsA, respectively. Only 116 axSpA patients (35.3%) had available Ankylosing Spondylitis Disease Activity Score (ASDAS) or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at bDMARD onset, of which 61 presented active disease. Disease Activity in PSoriatic Arthritis (DAPSA) or Disease Assessment Score - 28 joints (DAS-28) values at bDMARD onset were available for only 61 PsA (16.7%) patients, with 23 of them having active disease. The number of patients with available tender joint count or swollen joint count assessment was 68 (20.7%) and 59 (18%) for axSpA, and 115 (31.5%) and 119 (32.6%) for PsA, respectively. SEC was used in 63 (19.2%) axSpA patients and in 63 (17.3%) PsA patients. Conclusion: Using NLP, the study showed that around one-third of axSpA and one-sixth of PsA patients have disease activity assessments with ASDAS/BASDAI or DAPSA/DAS-28, respectively, highlighting an area of improvement in these patients' management.

Investigating axial spondyloarthritis and psoriatic arthritis patients using natural language processing We conducted a study in Spain to better understand patients with specific rheumatic conditions known as axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). To analyze their characteristics, we used a computer technology called EHRead, which uses Natural Language Processing (NLP) to analyze free text from electronic health records. Out of a large group of patients, we focused on 758 individuals who had axSpA or PsA. Most of the axSpA patients were men, and they were around 51 years old on average. For the PsA patients, most were women, and their average age was about 54 years. We analyzed outcomes and treatments of these patients. Our findings showed that we can describe and assess a cohort of patients from real world using NLP. Besides, only about one-third of axSpA patients and one-sixth of PsA patients had their respective outcomes completely assessed, which indicates that there is potential room for improvement in the management of axSpA and PsA. The most promising feature in our study is the use of NLP, an artificial intelligence technology that helps us understand information in medical records written in free text. This can help us explore the characteristics of patients and their management in the real world, bringing an opportunity to enhance the care of patients with axSpA and PsA.

Sex-related differences of cAMP-specific PDE4B3 mRNA in oligodendrocytes following systemic inflammation.

Sex-related differences have been observed in the incidence and severity of several neurological diseases and in sepsis in humans. Cyclic adenosine monophosphate (cAMP) has been shown to play an important role in modulating the inflammatory environment during neuroinflammation and importantly in protecting myelin from excitotoxic cell death. Considering the sexual dimorphism in the functional properties of oligodendrocytes and the importance of a systemic inflammation in the progression of multiple sclerosis, we focused on identifying possible sex-related differences in the alterations previously reported for the two phosphodiesterase4B (PDE4B) splice-variants (PDE4B2 and PDE4B3) mRNA expression during innate neuroinflammation. PDE4A, PDE4B, and PDE4D are present in oligodendrocytes and we have previously reported that PDE4B3 mRNA is readily expressed in both oligodendrocytes and neurons. In this study, we analyzed the influence of an intraperitoneal lipopolysaccharide injection on the distribution pattern and expression levels of the PDE4B mRNA splicing variants in both male and female mice brains. Clear differences were observed in PDE4B2 and PDE4B3 mRNA expression levels in males compared with females in a time-dependent manner. Furthermore, we observed that the clear downregulation of PDE4B3 mRNA was reflected in a lower percentage of oligodendrocytes positive for this transcript which correlated with a decrease in inducible cAMP early repressor expression in female corpus callosum.

Disease activity indexes might not capture the same disease aspects in males and females with ankylosing spondylitis: A real-world nationwide analysis.

Background: To evaluate gender differences in disease activity and health status (HS) in patients with radiographic axial spondyloarthritis (r-axSpA)/ankylosing spondylitis (AS). Methods: Ancillary analysis of the MIDAS study, an observational, non-interventional, cross-sectional and retrospective multicenter nationwide study to assess disease activity and its relationship with HS in clinical practice. Adult patients with AS diagnosis, fulfilling ASAS and modified New York criteria, treated for ≥3 months upon study inclusion according to clinical practice were included. The primary outcome was "disease control" assessed by the percentage of patients in remission and low disease activity (BASDAI and ASDAS-CRP scores). HS was evaluated using the ASAS health index (ASAS-HI). Patients' responses and characteristics were analyzed by gender. Results: We analyzed 313 patients with AS, 237 (75.7%) males and 76 (24.3%) females. A total of 202 (64.5%) patients had adequate disease control (BASDAI < 4); 69.2% of males [mean (SD) BASDAI 2.9 (2.1)] and 50.0% of females [mean (SD) BASDAI 3.8 (2.4); p = 0.01]. According to ASDAS-CRP, 57.5% of patients were adequately controlled (ASDAS-ID +ASDAS-LDA); 138 (58.2%) males and 42 (55.3%) females. The mean (SD) ASDAS-CRP was 1.9 (1.1); being 1.9 (1.0) in males and 2.0 (1.1) in females. Overall, the impact of AS on HS was low to moderate [mean (SD) ASAS-HI 5.8 (4.4)]; being 5.5 (4.4) for males and 6.8 (4.2) for females (p = 0.02). Conclusion: This study showed a higher proportion of females with AS and active disease using the BASDAI definition. When using the ASDAS-CRP definition these differences by gender were less pronounced. The impact of disease activity on HS appears to be higher in females than males.

Lipopolysaccharide administration in vivo induces differential expression of cAMP-specific phosphodiesterase 4B mRNA splice variants in the mouse brain.

Many inflammatory processes involve cAMP. Pharmacological manipulation of cAMP levels using specific phosphodiesterase (PDE) inhibitors provokes an antiinflammatory response. The aim of this study was to investigate changes in the pattern and levels of expression of mRNAs coding for the cAMP-specific PDE4 family and subfamilies in mouse brain during the immediate acute immune response provoked by an intraperitoneal injection of lipopolysaccharide (LPS). PDE4B, and furthermore the splice variants PDE4B2 and PDE4B3, were the only mRNAs that showed altered expression. Whereas PDE4B2 presented increased expression at both 3 and 8 hr postinjection, PDE4B3 mRNA showed decreased expression that reached a minimum 8 hr postinjection. PDE4B2 mRNA upregulation was observed mainly in endothelial and macrophage/neutrophil cell populations in the leptomeninges, and the downregulation of PDE4B3 was observed mainly in oligodendrocytes throughout the brain. Our results clearly illustrate the distinctive anatomical distribution and cellular localization of the PDE4Bs during neuroinflammation and emphasize the importance of PDE4B splice-variant-specific inhibitors as therapeutic tools.

Critical role for PDE4 subfamilies in the development of experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis exhibiting neuroinflammation, axonal damage and demyelination, further characterized by T- and B-cell responses to myelin oligodendrocyte glycoprotein. Pharmacological manipulation of phosphodiesterases (PDEs) provokes profound anti-inflammatory responses through modulation of cAMP levels. The PDE4B subfamily has been related to the inflammatory immune response in mice and PDE4 inhibition produces amelioration of the clinical signs and delayed onset in the EAE model. Analyses of the expression of the mRNA coding for PDE4B splice variants revealed an upregulation of PDE4B2 in the brainstem and spinal cord of EAE mice which correlated with forkhead box P3 (FoxP3) and transforming growth factor beta (TGF-ß) mRNAs expression in a score-dependent manner. The increase observed for the PDE4B protein was mainly found in antigen-presenting cells (APCs) such as dendritic cells and microglia/macrophages, in areas with high cellular infiltration. Unexpectedly, PDE4B(-/-) mice showed an earlier onset of the disease compared to wildtype mice. The results point to a possible role of the PDE4B enzyme and in particular the PDE4B2 splice variant during EAE pathogenesis, probably by modulating cAMP levels in APCs, consequently influencing the cytokine environment important for T-cell differentiation.

Disease control in patients with ankylosing spondylitis in real clinical practice in Spain: Results of the MIDAS study / Control de la enfermedad en pacientes con espondilitis anquilosante en la práctica clínica habitual en España: Resultados del estudio MiDAS

Introduction and objectives: Understanding the disease activity is fundamental to improve patient prognosis and patients’ quality of life. MiDAS study described disease activity in ankylosing spondylitis (AS) Spanish patients and the proportion of them with controlled disease. Methods: Observational, cross-sectional, multicenter study carried out under conditions of routine clinical practice. Adult (≥18 years) patients with ≥6 months since AS diagnosis treated ≥3 months prior to inclusion. The primary endpoint was the percentage of patients with low disease activity assessed through BASDAI (primary endpoint) and ASDAS-CRP (secondary endpoint). Results: 313 AS patients included: 75.7% male; 78.5% HLA-B*27 positive; mean (SD) baseline age of 50.4 (12.0) years; mean (SD) disease duration of 15.5 (11.6) years; 73.5% were treated with biological disease-modifying antirheumatic drugs (DMARDs), 22.4% with non-biological DMARDs and 53.7% with non-steroidal anti-inflammatory drugs, alone or in combination. Monotherapy with biologics and non-biologics was used by 29.7% and 26.8% of patients, respectively. According to BASDAI, 38.0% were in remission (BASDAI≤2) and 64.5% showed adequate disease control (BASDAI<4). According to ASDAS-CRP, 29.4% achieved remission (ASDAS-CRP<1.3) and 28.1% low disease activity (1.3≤ASDAS-CRP<2.1). Conclusions: Almost two thirds of the AS patients recruited had low disease activity, with about one third of them being in remission (BASDAI≤2, ASDAS-CRP<1.3). These results highlight the existing room for improvement in treating AS patients in clinical practice.(AU)

Introducción y objetivos: Comprender la actividad de la enfermedad es fundamental para mejorar el pronóstico y la calidad de vida de los pacientes. El estudio MiDAS describió la actividad de la enfermedad en pacientes españoles con espondilitis anquilosante (EA) y la proporción de ellos con enfermedad controlada. Métodos: Estudio observacional, transversal, multicéntrico, realizado en condiciones de práctica clínica habitual. Pacientes adultos (≥18años) con ≥6meses desde el diagnóstico de EA tratados ≥3meses antes de la inclusión. La variable principal fue el porcentaje de pacientes en baja actividad, evaluado mediante BASDAI (variable principal) y ASDAS-CRP (variable secundaria). Resultados: Hubo 313 pacientes con EA incluidos: 75,7% varones; 78,5% HLA-B*27 positivos; edad media (DE) basal de 50,4 (12,0) años; duración media (DE) de la enfermedad de 15,5 (11,6) años; el 73,5% fueron tratados con fármacos antirreumáticos modificadores de la enfermedad (FAME) biológicos, el 22,4% con FAME no biológicos y el 53,7% con antiinflamatorios no esteroideos, solos o en combinación. La monoterapia con biológicos y no biológicos fue utilizada por el 29,7 y el 26,8% de los pacientes, respectivamente. Según BASDAI, el 38,0% estaban en remisión (BASDAI≤2) y el 64,5% mostraron un adecuado control de la enfermedad (BASDAI<4). Según ASDAS-CRP, el 29,4% alcanzaron remisión (ASDAS-CRP<1,3) y el 28,1% baja actividad de la enfermedad (1,3≤ASDAS-CRP<2,1). Conclusiones: Casi dos tercios de los pacientes con EA incluidos presentaban baja actividad de la enfermedad, con aproximadamente un tercio de ellos en remisión (BASDAI≤2, ASDAS-CRP<1,3). Estos resultados destacan el margen de mejora existente para tratar pacientes con EA en la práctica clínica.(AU)

Disease control in patients with psoriatic arthritis in real clinical practice in Spain: MiDAS study / Control de la enfermedad en pacientes con artritis psoriásica en práctica clínica real en España: estudio MiDAS

Objective: MiDAS study assessed the percentage of psoriatic arthritis (PsA) patients treated in routine clinical practice who achieved control of disease activity according to Disease Activity in Psoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA). Methods: Observational, non-interventional, cross-sectional, multicenter study conducted under conditions of routine clinical practice in 36 centers with outpatient rheumatology clinics in Spanish public hospitals. Patients included were adults (≥18 years) with ≥6 months PsA diagnosis according to classification for PsA (CASPAR) criteria and undergoing treatment ≥3 months. The main variable evaluated was the percentage of patients under remission and low disease activity, assessed through DAPSA and MDA. Results: 313 patients with PsA were included: 54.3% male; with mean age of 54.1±12.2 years and mean disease duration of 10.5±9.0 years. Mean C-reactive protein (CRP) serum levels were 4.9±7.3mg/L. At the study visit, 58.5% of patients were in monotherapy (17.6% biological and 40.9% non-biological) and 41.2% were receiving biological and non-biological therapy. 59.4% of patients showed low disease activity (DAPSA≤14) and 19.8% were on remission (DAPSA≤4). Moreover, 51.4% of the patients reached an MDA status (≥5 MDA). Conclusions: Around 40% of PsA patients presented uncontrolled disease, highlighting the need to improve the management of these patients in clinical practice.(AU)

Objetivo: El estudio MiDAS evaluó el porcentaje de pacientes con artritis psoriásica (APs) tratados en práctica clínica habitual que lograron el control de la actividad de la enfermedad de acuerdo con Disease Activity in Psoriatic Arthritis (DAPSA) y Minimal Disease Activity (MDA). Métodos: Estudio observacional, no intervencionista, transversal, multicéntrico, realizado en condiciones de práctica clínica habitual en 36 centros con consultas externas de reumatología de hospitales públicos españoles. Los pacientes incluidos eran adultos (≥18 años) con ≥6 meses de diagnóstico de APs según los criterios de clasificación de la APs (CASPAR) y en tratamiento durante ≥3 meses. La variable principal evaluada fue el porcentaje de pacientes en remisión y baja actividad de la enfermedad, evaluados mediante DAPSA y MDA. Resultados: Se incluyeron 313 pacientes con APs: 54,3% varones; con una edad media de 54,1±12,2 años y una duración media de la enfermedad de 10,5±9,0 años. Los niveles séricos medios de proteína C reactiva fueron de 4,9±7,3mg/L. En la visita del estudio, el 58,5% de los pacientes estaban siendo tratados con monoterapia (17,6% biológicos y 40,9% no biológicos) y el 41,2% recibían terapia biológica y no biológica. El 59,4% de los pacientes mostró baja actividad de la enfermedad (DAPSA≤14) y el 19,8% estaban en remisión (DAPSA≤4). Además, el 51,4% de los pacientes alcanzó un estado de MDA (≥5 MDA). Conclusiones: Alrededor del 40% de los pacientes con APs presentaban enfermedad no controlada, destacando la necesidad de mejorar el manejo de estos pacientes en la práctica clínica.(AU)

Neuroanatomical distribution and neurochemical characterization of cells expressing adenylyl cyclase isoforms in mouse and rat brain.

Transmembrane adenylyl cyclases (Adcy) are involved in the regulation of multiple brain processes such as synaptic plasticity, learning and memory. They synthesize intracellular cyclic adenosine monophosphate (cAMP) following activation by G-protein coupled receptors. We examined the neuroanatomical distribution of the nine Adcy isoforms in rat and mouse brain by in situ hybridization, as well as their location in glutamatergic, GABAergic and cholinergic neurons in several mouse brain areas by double in situ hybridization. The Adcys are widely distributed throughout the brain in both rat and mouse, being especially abundant in cortex, hippocampus, thalamic nuclei, the olfactory system and the granular layer of the cerebellum. Double-labeling experiments showed that Adcy isoforms are differently expressed in glutamatergic, GABAergic and cholinergic neuronal cell populations. We report the neuroanatomical distribution of the nine known Adcy isoforms in rat and mouse brain and their cellular localization.