Niveles elevados de leptina y adipsina se asocian con la actividad clínica en pacientes con artritis reumatoide temprana con sobrepeso e infección periodontal

Las adipocinas están asociadas a la patogénesis de la artritis reumatoide (AR) y son biomarcadores potenciales de la actividad de la enfermedad, la periodontitis y la obesidad. El objetivo era establecer la asociación entre el perfil de adipocinas, la actividad de la enfermedad de la AR, el índice de masa corporal y la infección periodontal. En este estudio se evaluaron 51 pacientes con AR temprana y 51 controles, incluyendo marcadores reumatológicos séricos, niveles de adipocinas, detección de Porphyromonas gingivalis y anticuerpos séricos anti-Porphyromonas gingivalis, y mediciones clínicas y periodontales. Se realizaron análisis estadísticos con SPSS® V26, con un modelo de regresión logística para confirmar las asociaciones. Los resultados muestran que los niveles elevados de leptina eran más frecuentes en pacientes (p = 0,001) que presentaban simultáneamente una mayor frecuencia de Porphyromonas gingivalis (p = 0,004). Los pacientes con presencia concomitante de Porphyromonas gingivalis, alta puntuación de actividad clínica y sobrepeso se correlacionaron con altos niveles de leptina (OR, 7,20; IC 95%, 2,68-19,33; p = 0,0001) y adipsina (OR, 2,69; IC 95%, 1,00-7,28; p = 0,005). La conclusión es que los niveles elevados de leptina y adipsina se asocian a una mayor actividad clínica en pacientes con AR temprana con sobrepeso e infección periodontal, por lo que el sobrepeso y Porphyromonas gingivalis pueden potenciar la actividad de la AR. Esto puede representar un mecanismo patológico entre estas condiciones, donde las adipokinas parecen tener un papel clave.Adipokines are associated with the pathogenesis of rheumatoid arthritis (RA) and are potential biomarkers of disease activity, periodontitis, and obesity. The aim of this was to establish the association between adipokine profile, RA disease activity, body mass index, and periodontal infection. This study evaluated 51 patients with early-RA and 51 controls including serum rheumatological markers, adipokine levels, detection of Porphyromonas gingivalis and serum anti-Porphyromonas gingivalis antibodies, clinical and periodontal measurements. Statistical analyses were run with SPSS® V26, with a logistic regression model to confirm associations. The results show high levels of leptin were more frequent in patients (p = 0.001) who simultaneously showed a higher frequency of Porphyromonas gingivalis (p = 0.004). Patients with concomitant presence of Porphyromonas gingivalis, high clinical activity score, and overweight were correlated with high levels of leptin (OR, 7.20; 95% CI, 2.68–19.33; p = 0.0001) and adipsin (OR, 2.69; 95% CI, 1.00–7.28; p = 0.005). The conclusion is that high levels of leptin and adipsin are associated with greater clinical activity in early-RA patients with overweight and periodontal infection, whereby overweight and Porphyromonas gingivalis may enhance RA activity. This may represent a pathological mechanism between these conditions, where adipokines seem to have a key role

Predictors of response to etanercept-methotrexate treatment: a post hoc logistic regression analysis of a randomized, open-label study in Latin American patients with rheumatoid arthritis

Background: Determining potential predictors of clinical response would allow a more personalized rheumatoid arthritis (RA) treatment approach in heterogeneous populations such as Latin American (LA) patients. Methods: Post hoc analysis to identify baseline characteristics predictive of clinical remission in response to treatment with etanercept (ETN) plus methotrexate (MTX) in LA patients with moderate to severe MTX-resistant RA. We report data from the group of patients who received ETN 50 mg/week plus MTX (ETN + MTX, n = 281) in a clinical trial consisting of an initial 24-week open-label phase, followed by a 104-week extension. Remission was defined as 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) score  28.5 kg/m2 (OR 3.24), disease duration > 3.7 years (OR 2.22), ESR ≤ 42 mm/h (OR 2.72), PGA ≤ 6 (OR 3.21), tender joint count ≤ 14 (OR 2.25), and total HAQ score ≤ 1.6 (OR 2.86). At Week 128, age ≤ 42 years (OR 2.21), SF-36 Mental Health Scale score > 39.6 (OR 2.16), White race (OR 4.07), > 18 swollen joints (OR 2.11), and VAS Pain ≤ 41 (OR 6.05) at baseline were the best subset of significant predictors of remission. Conclusions In LA patients with RA, younger age, higher BMI, longer disease duration, higher SF-36 Mental Health Scale score, higher swollen joint count, and overall lower disease activity predicted clinical response to ETN + MTX therapy

El efecto de interacción de los títulos de anticuerpos anti-RgpA y anti-PPAD: Un indicador para el diagnóstico de la artritis reumatoide

Porphyromonas gingivalis secreta factores de virulencia como Arg-gingipains y peptidil arginina deiminasa (PPAD), que están asociados con la patogénesis de la artritis reumatoide (AR). Sin embargo, no existe información sobre los títulos de anticuerpos frente a estas enzimas bacterianas como indicadores sistémicos o biomarcadores en la AR. En este estudio transversal se evaluó a 255 individuos: 143 con diagnóstico de AR y 112 sin AR. Se utilizaron modelos de regresión logística ajustados por edad, sexo, índice metabólico basal, tabaquismo y gravedad de la periodontitis para evaluar la asociación de la AR con el factor reumatoide (FR), los anticuerpos antiproteínas citrulinadas (ACPA), la velocidad de sedimentación globular, la proteína C reactiva de alta sensibilidad, los anti-RgpA, los anti-PPAD y los anti-RgpA/anti-PPAD doblemente positivos. Se observó que el FR (odds ratio [OR] 10,6; intervalo de confianza [IC] del 95%: 4,4-25), los ACPA (OR 13,7; IC del 95%: 5,1-35) y la doble positividad anti-RgpA/anti-PPAD (OR 6,63; IC del 95%: 1,61-27) se asociaban con el diagnóstico de AR. Los anti-RgpA también se asociaron con la AR (OR 4,09; IC 95%: 1,2-13,9). La combinación de anti-RgpA/anti-PPAD mostró una elevada especificidad del 93,7% y un VPP del 82,5% en la identificación de individuos con AR. Los anticuerpos anti-RgpA se asociaron con el índice inflamatorio periodontal en individuos con AR (p < 0,05). La doble positividad de los anticuerpos anti-RgpA/anti-PPAD mejoró el diagnóstico de AR. Por lo tanto, los anticuerpos RgpA y anti-RgpA/anti-PPAD pueden ser biomarcadores de la AR.Porphyromonas gingivalis secretes virulence factors like Arg-gingipains and peptidyl arginine deiminase (PPAD), that are associated with rheumatoid arthritis (RA) pathogenesis. However, there is no information regarding the antibody titers for these bacterial enzymes as systemic indicators or biomarkers in RA. In this cross-sectional study, 255 individuals were evaluated: 143 were diagnosed with RA, and 112 were without RA. Logistic regression models adjusted for age, sex, basal metabolic index, smoking, and periodontitis severity were used to evaluate the association of RA with rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs), erythrocyte sedimentation rate, high sensitivity C-reactive protein, anti-RgpA, anti-PPAD, and double positive anti-RgpA/anti-PPAD. It was found that RF (odds ratio [OR] 10.6; 95% confidence interval [CI] 4.4–25), ACPAs (OR 13.7; 95% CI 5.1–35), and anti-RgpA/anti-PPAD double positivity (OR 6.63; 95% CI 1.61–27) were associated with RA diagnoses. Anti-RgpA was also associated with RA (OR 4.09; 95% CI 1.2–13.9). The combination of anti-RgpA/anti-PPAD showed a high specificity of 93.7% and 82.5% PPV in identifying individuals with RA. RgpA antibodies were associated with the periodontal inflammatory index in RA individuals (p < 0.05). The double positivity of the anti-RgpA/anti-PPAD antibodies enhanced the diagnosis of RA. Therefore, RgpA antibodies and anti-RgpA/anti-PPAD may be biomarkers for R

Aplicación de criterios de cribado de la enfermedad inflamatoria intestinal en pacientes con espondiloartritis y su asociación con la enfermedad y la actividad endoscópica

Existe poca bibliografía sobre la aplicación de criterios de cribado de la enfermedad inflamatoria intestinal (EII) en pacientes con espondiloartritis (EPS). Este estudio tenía como objetivo aplicar criterios de cribado de EII en un grupo de pacientes con EspA sin diagnóstico de EII y correlacionarlos con los hallazgos endoscópicos y la actividad de la enfermedad. Se incluyó a un total de 82 pacientes con EspA. Se realizó la prueba de cribado de la EII y una ileocolonoscopia con cromoendoscopia digital con aumento y análisis histológico. Los datos se analizaron con la prueba de Chi-cuadrado/prueba exacta de Fisher y análisis de correspondencias múltiples. Los principales criterios de cribado encontrados en el 48,7% de los pacientes estaban asociados a antecedentes de infección (p = 0,037). La hemorragia rectal se asoció al diagnóstico de espondilitis anquilosante, inflamación aguda, entesitis y alteración de la arquitectura tisular en el íleon (p < 0,050). La diarrea se asoció a una mayor puntuación de la actividad de la enfermedad (p = 0,02). Los criterios de cribado menores se asociaron con una articulación inflamatoria dolorosa (p = 0,05), una puntuación elevada de la actividad de la enfermedad (p = 0,001) y niveles elevados de calprotectina (p = 0,050). El dolor abdominal (36,9%) se asoció con compromiso axial/periférico (p = 0,017), dolor lumbar inflamatorio (p = 0,01), entesitis (p = 0,021), mayor puntuación de actividad de la enfermedad (p = 0,023) e inflamación aguda del íleon (p = 0,046). La diarrea de 4 semanas y el dolor abdominal fueron los criterios de cribado mayor y menor más prevalentes, respectivamente, estando relacionados con manifestaciones tempranas de compromiso inflamatorio intestinal y mayor puntuación de actividad de la enfermedad. Esta prueba de cribado ofrece la posibilidad de derivar oportunamente a los pacientes con EAE de reumatología a gastroenterología.There is little literature on the implementation of screening criteria for inflammatory bowel disease (IBD) in patients with spondyloarthritis (SpA). This study aimed to apply IBD screening criteria in a group of patients with SpA without IBD diagnosis and correlate them to endoscopic findings and disease activity. A total of 82 patients with SpA were included. The IBD screening test and ileocolonoscopy with digital chromoendoscopy with magnification and histological analysis were performed. The data were analysed with Chi-square test/Fisher’s exact test and multiple correspondence analysis. The major screening criteria found in 48.7% of the patients were associated with a history of infection (p = 0.037). Rectal bleeding was associated with the diagnosis of ankylosing spondylitis, acute inflammation, enthesitis and tissue architecture alteration in the ileum (p < 0.050). Diarrhoea was associated with a higher disease activity score (p = 0.02). Minor screening criteria were associated with painful inflammatory joint (p = 0.05), high disease activity score (p = 0.001) and high calprotectin levels (p = 0.050). Abdominal pain (36.9%) was associated with axial/peripheral compromise (p = 0.017), inflammatory back pain (p = 0.01), enthesitis (p = 0.021), higher disease activity score (p = 0.023) and acute ileum inflammation (p = 0.046). Diarrhoea of 4 weeks and abdominal pain were the most prevalent major and minor screening criteria, respectively, being related to early manifestations of inflammatory bowel compromise and higher disease activity score. This screening test grants a chance of opportune referral of SpA patients from rheumatology to gastroenterology

Upadacitinib in patients with psoriatic arthritis and an inadequate response to non-biological therapy: 56-week data from the phase 3 SELECT-PsA 1 study

Background: In SELECT-PsA 1, a randomised double-blind phase 3 study, upadacitinib 15 mg and 30 mg were superior to placebo and non-inferior to adalimumab in ≥20% improvement in American College of Rheumatology (ACR) criteria at 12 weeks in patients with psoriatic arthritis (PsA). Here, we report 56-week efficacy and safety in patients from SELECT-PsA 1. Methods: Patients received upadacitinib 15 mg or 30 mg once daily, adalimumab 40 mg every other week for 56 weeks or placebo through week 24 switched thereafter to upadacitinib 15 mg or 30 mg until week 56. Efficacy endpoints included the proportion of patients achieving ≥20%/50%/70% improvement in ACR criteria (ACR20/50/70), ≥75%/90%/100% improvement in Psoriasis Area and Severity Index (PASI75/90/100), minimal disease activity (MDA) and change from baseline in modified total Sharp/van der Heijde Score. Treatment-emergent adverse events per 100 patient years (PY) were summarised. Results: Consistent with results through week 24, ACR20/50/70, PASI75/90/100 and MDA responses were maintained with upadacitinib through week 56 and were generally numerically higher than with adalimumab; inhibition of radiographic progression was also maintained. Patients who switched from placebo to upadacitinib exhibited comparable improvements at week 56 as patients originally randomised to upadacitinib. The rates of serious adverse events were 9.1 events/100 PY with upadacitinib 15 mg and 12.3 events/100 PY with upadacitinib 30 mg. Two deaths were reported in each of the upadacitinib groups. Conclusion: Efficacy across various domains of PsA were maintained with upadacitinib 15 mg and 30 mg through week 56 with no new safety signals observed

The Danger Model Approach to the Pathogenesis of the Rheumatic Diseases

The danger model was proposed by Polly Matzinger as complement to the traditional self-non-self- (SNS-) model to explain the immunoreactivity. The danger model proposes a central role of the tissular cells’ discomfort as an element to prime the immune response processes in opposition to the traditional SNS-model where foreignness is a prerequisite. However recent insights in the proteomics of diverse tissular cells have revealed that under stressful conditions they have a significant potential to initiate, coordinate, and perpetuate autoimmune processes, in many cases, ruling over the adaptive immune response cells; this ruling potential can also be confirmed by observations in several genetically manipulated animal models. Here, we review the pathogenesis of rheumatic diseases such as systemic lupus erythematous, rheumatoid arthritis, spondyloarthritis including ankylosing spondylitis, psoriasis, and Crohn’s disease and provide realistic approaches based on the logic of the danger model. We assume that tissular dysfunction is a prerequisite for chronic autoimmunity and propose two genetically conferred hypothetical roles for the tissular cells causing the disease: (A) the Impaired cell and (B) the paranoid cell. Both roles are not mutually exclusive. Some examples in human disease and in animal models are provided based on current evidence

Síndrome de hiperuricemia: Una perspectiva fisiopatológica integrada

Hyperuricemia syndrome is relatively common in humans, affecting nearly a quarter of the population, with male predominance 3 to 4 times higher comparing with premenopausal women. Most patients with hyperuricemia (>90%) only show this finding without any evidence of symptomatology; however, the rest do have some clinical picture, being the most common gout.Uric acidmetabolismis complex,which causes its involvemnt in other conditions either directly or indirectly, either as a cause or consequently thereof. In this work we made a conceptual integration between the etiological, pathophysiological and clinical bases of this syndrome.El síndrome hiperuricémico es relativamente común en el ser humano, ya que afecta a casi una cuarta parte de la población, con una predominancia en los varones 3 a 4 veces mayor respecto a las mujeres premenopáusicas. La gran mayoría de los pacientes con hiperuricemia (>90%) solo muestran este hallazgo sin evidencia de sintomatología; sin embargo, el resto de ellos sí adolece de algún cuadro clínico, siendo el más frecuente la gota. El metabolismo del ácido úrico es complejo, lo que ocasiona su involucro en otras afecciones, ya sea directa o indirectamente, ya sea como causa o consecuencia de estos. En este trabajo hicimos una integración conceptual entre las bases etiológicas, fisiopatogénicas y clínicas de este síndrome

VX-509 (Decernotinib), an Oral Selective JAK-3 Inhibitor, in Combination With Methotrexate in Patients With Rheumatoid Arthritis

ObjectiveTo assess the efficacy and safety of decernotinib (VX-509), an oral selective inhibitor of JAK-3, in patients with rheumatoid arthritis (RA) in whom the response to methotrexate treatment was inadequate. MethodsIn this 24-week, double-blind, randomized phase IIb study, 358 patients with active RA received either placebo (n=71) or VX-509 at dosages of 100 mg/day (n=71), 150 mg/day (n=72), 200 mg/day (n=72), or 100 mg twice daily (n=72). Primary measures of efficacy at week 12 were the response rate according to the American College of Rheumatology 20% improvement criteria (ACR20) and change from baseline in the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP). ResultsAt week 12, the ACR20 response rates were 46.5%, 66.7%, 56.9%, and 68.1% in the groups receiving VX-509 at dosages of 100 mg/day, 150 mg/day, 200 mg/day, and 100 mg twice daily, respectively, and 18.3% in the placebo group (P <0.001 for all comparisons). At week 12, the mean change from baseline in the DAS28-CRP was significantly greater in each VX-509 group compared with the placebo group (P <0.001). Improvements were maintained at week 24, as shown by the ACR20, ACR50, and ACR70 response rates and mean change from baseline in the DAS28-CRP. The most common adverse event in the VX-509 group was headache (8.7%), and elevated levels of transaminases, lipoproteins, and creatinine were observed. ConclusionVX-509 significantly improved the signs and symptoms of RA at weeks 12 and 24 compared with the placebo group when it was administered in combination with methotrexate. Safety signals included infection and increases in liver transaminase and lipid level

Inflammatory foot involvement in spondyloarthritis : from tarsitis to ankylosing tarsitis

Spondyloarthritis (SpA) is a group that includes a wide spectrum of clinically similar diseases manifested by oligoarticular arthritis and axial or peripheral ankylosis. Although axial SpA is predominant in Caucasians and adult-onset patients, juvenile-onset and Latin American patients are characterized by severe peripheral arthritis and particularly foot involvement. The peripheral involvement of SpA can vary from tarsal arthritis to the most severe form named ankylosing tarsitis (AT). Although the cause and etiopathogenesis of axSpA are often studied, the specific characteristics of pSpA are unknown. Several animal models of SpA develop initial tarsitis and foot ankylosis as the main signs, emphasizing the role of foot inflammation in the overall SpA spectrum. In this review, we attempt to highlight the clinical characteristics of foot involvement in SpA and update the knowledge regarding its pathogenesis, focusing on animal models and the role of mechanical forces in inflammation