Editorial II

La inflamación espinal es una de las más importantes características de la espondilitis anquilosante (EA), ya que determina el dolor y la disfunción espinal. Actualmente, la inflamación de la columna se evalúa principalmente a través de los pacientes informados resultados y puede estar sujeto a factores individuales e interferencias. Las imágenes por resonancia magnética (IRM) han demostrado su valor en la detección de edema e inflamación ósea y han sido incluidas en los nuevos criterios de Evaluación de la Sociedad Internacional de Espondiloartritis (ASAS). Poco a poco, la resonancia se impuso debido a su mayor sensibilidad en comparación con Rayos X, especialmente en lesiones tempranas y en ensayos clínicos

Diagnostic value of MRI of the sacroiliac joints in juvenile spondyloarthritis

Early diagnosis of spondyloarthritis (SpA) is becoming more important as new medical treatment options have become available to treat inflammation and delay progression of the disease. Increasingly, magnetic resonance imaging (MRI) of the sacroiliac joints is obtained for early detection of inflammatory changes, as it shows active inflammatory and structural lesions of sacroiliitis long before radiographic changes become evident. MRI of the sacroiliac joints in children is a useful tool for suspected juvenile spondyloarthritis (JSpA), even though it is not yet included in the current pediatric classification systems. Recognizing MRI features of pediatric sacroiliitis is a challenge. As most radiologists are not familiar with the normal MRI appearance of the pediatric sacroiliac joint, clear definitions are mandatory. Actually, the adult Assessment of Spondyloarthritis International Society (ASAS) definition for sacroiliitis needs some adaptations for children. A proposal for a possible pediatric-specific definition for active sacroiliitis on MRI is presented in this review. Furthermore, MRI without contrast administration is sufficient to identify bone marrow edema (BME), capsulitis, and retroarticular enthesitis as features of active sacroiliitis in JSpA. In selected cases, when high short tau inversion recovery (STIR) signal in the joint is the only finding, gadolinium-enhanced images may help to confirm the presence of synovitis. Lastly, we found a high correlation between pelvic enthesitis and sacroiliitis on MRI of the sacroiliac joints in children. As pelvic enthesitis indicates active inflammation, it may play a role in assessment of the inflammatory status. Therefore, it should be carefully sought and noted when examining MRI of the sacroiliac joints in children

Added Value of Anti-CD74 Autoantibodies in Axial SpondyloArthritis in a Population With Low HLA-B27 Prevalence

Axial spondyloarthritis (axSpA) is often diagnosed late due to the non-specific nature of its main symptom [chronic back pain (CBP)] and to the paucity of diagnostic markers, particularly in regions with low HLA-B27 prevalence, such as the Middle-East. We tested the performance of IgG4 and IgA anti-CD74 antibodies as an early diagnostic marker for axSpA, compared with the performance of HLA-B27, in Lebanon. Sera of axSpA patients diagnosed by the rheumatologist and also fulfilling the imaging arm of the ASAS criteria (patients) and of blood donors (BD) (controls) were analyzed for HLA-B27, IgG4 and IgA anti-CD74, blinded to clinical characteristics. Receiver Operating Characteristic curves were constructed to identify an optimal cut-off point for anti-CD74 antibodies. Diagnostic properties were calculated (sensitivity, specificity, positive, and positive predictive values (PPV, NPV), Likelihood ratios) for each marker. Forty-nine axSpA patients and 102 BD were included in the final analysis. IgA anti-CD74 correlated poorly with axSpA (Area Under the Curve (AUC) 0.657), whereas IgG4 anti-CD74 had a good discriminative value (AUC 0.837). Respectively, for HLA-B27, IgG4 anti-CD74, and the combination of both, we found a sensitivity of 33-92-33%, specificity of 96-79-98%, PPV 80-68-89%, NPV 75-95-75%, and LR+ 8.2-4.4-16.5. IgG4 anti-CD 74 were positive in 88% of HLA-B27 negative axSpA patients, and correlated with BASDAI. In this first study in a population with low HLA-B27 prevalence, IgG4 anti-CD74 antibodies combined with HLA-B27 showed higher diagnostic value than HLA-B27 alone for early axSpA. IgG4 anti-CD74 should be considered for further evaluation as an early axSpA diagnostic marker in future dedicated research, particularly in patients with CBP

ASAS definition for sacroiliitis on MRI in SpA : applicable to children?

Background: The Assessment of Spondyloarthritis International Society (ASAS) definition for a'positive' Magnetic Resonance Imaging (MRI) for sacroiliitis is well studied and validated in adults, but studies about the value of this definition in children are lacking. The aim of this study is to evaluate whether the adult ASAS definition of a positive MRI of the sacroiliac joints can be applied to children with a clinical suspicion of Juvenile Spondyloarthritis (JSpA). Methods: Two pediatric musculoskeletal radiologists blinded to clinical data independently retrospectively reviewed sacroiliac (SI) joint MRI in 109 children suspected of sacroiliitis. They recorded global impression (sacroiliitis yes/no) and whether the adult ASAS definition for sacroiliitis was met at each joint. This was compared to goldstandard clinical diagnosis of JSpA. Additionally, MRI were scored according to'adapted' ASAS definitions including other features of sacroiliitis on MRI. Results: JSpA was diagnosed clinically in 47/109 (43%) patients. On MRI, sacroiliitis was diagnosed by global assessment in 30/109 patients, of whom 14 also fulfilled ASAS criteria. No patients with negative global assessment for sacroiliitis fulfilled ASAS criteria. Sensitivity (SN) for JSpA was higher for global assessment (SN = 49%) than for ASAS definition (SN = 26%), but the ASAS definition was more specific (SP = 97% vs. 89%). Modifying adult ASAS criteria to allow bone marrow edema (BME) lesions seen on only one slice, synovitis or capsulitis, increased SN to 36%, 32% and 32% respectively, only slightly lowering SP. Including structural lesions increased SN to 28%, but lowered specificity to 95%. Conclusion: The adult ASAS definition for sacroiliitis has low sensitivity in children. A pediatric-specific definition of MRI-positive sacroiliitis including BME lesions visible on one slice only, synovitis and/or capsulitis may improve diagnostic utility, and increase relevance of MRI in pediatric rheumatology practice

TYK2 inhibition and its potential in the treatment of chronic inflammatory immune diseases

Immune-mediated chronic inflammatory diseases have emerged as a leading cause of morbidity and mortality in Western countries over the last decades. Although multiple putative factors have been suspected to be causally related to the diseases, their overarching etiology remains unknown. This review article summarizes the current state of scientific knowledge and understanding of the role of non-receptor tyrosine kinases, with a special focus on the Janus kinase TYK2 in autoimmune and immune mediated diseases as well as on the clinical properties of its inhibition. A panel of experts in the field discussed the scientific evidence and molecular rationale for TYK2 inhibition and its clinical application. Reviewing this meeting, we aim at providing an integrated overview of the clinical profile of TYK2 inhibition and its potential in targeted pharmacological therapy of chronic autoimmune and immune-mediated diseases, with a special focus on inflammatory diseases of the skin

¿Permiten los entrenamientos de resonancia magnética en espondiloartritis mejorar la performance de los reumatólogos para el reconocimiento de secuencias y lesiones?

Introducción: la resonancia magnética (RM) es una herramienta diagnóstica fundamental en la espondiloartritis (EspA) axial. Objetivo: estimar el porcentaje de aciertos en el reconocimiento de lesiones en RM de EspA y conocimientos teóricos, antes y después de realizar una intervención educativa. Estimar si la buena performance en los test se asocia a características individuales de los médicos. Materiales y métodos: estudio analítico, con intervención activa, se midieron los resultados antes y después de un test con 10 preguntas antes y después del desarrollo de un taller de imágenes de RM en EspA en ciudades distintas de Argentina. Se consideró buena performance a quienes lograron más de 12 puntos entre las dos evaluaciones. Resultados: se evaluaron en total 106 médicos. Los resultados de los test (total 10 preguntas) antes y después del taller fueron 53% de respuesta correctas y 68% respectivamente (p: 0.000). El 65% de los médicos alcanzaron una buena performance (más de 12 respuesta correctas). Conclusión: el porcentaje de aciertos fue mayor después del taller en forma general, la buena performance no se asoció a ninguna característica especifica de los médicos evaluados

results of the randomized, placebo-controlled GO-RAISE study

Background In the present study, we evaluated relationships between serum biomarkers and clinical/magnetic resonance imaging (MRI) findings in golimumab-treated patients with ankylosing spondylitis. Methods In the GO- RAISE study, 356 patients with ankylosing spondylitis randomly received either placebo (n = 78) or golimumab 50 mg or 100 mg (n = 278) injections every 4 weeks through week 24 (placebo-controlled); patients continuing GO-RAISE received golimumab through week 252. Up to 139/125 patients had sera collected for biomarkers/serial spine MRI scans (sagittal plane, 1.5-T scanner). Two blinded readers employed modified ankylosing spondylitis spine magnetic resonance imaging score for activity (ASspiMRI-a) and ankylosing spondylitis spine magnetic resonance imaging score for chronicity. Spearman correlations (r s) were assessed between serum biomarkers (n = 73) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), C-reactive-protein (CRP)-based Ankylosing Spondylitis Disease Activity Score (ASDAS), modified Stokes Ankylosing Spondylitis Spine Score (mSASSS), and ASspiMRI scores. Serum biomarkers predicting postbaseline spinal fatty lesion development and inflammation were analyzed by logistic regression. Results Significant, moderately strong correlations were observed between baseline inflammatory markers interleukin (IL)-6, intracellular adhesion molecule-1, complement component 3 (C3), CRP, haptoglobin, and serum amyloid-P and baseline ASDAS (r s = 0.39–0.66, p ≤ 0.01). Only baseline leptin significantly correlated with ASDAS improvement at week 104 (r s = 0.55, p = 0.040), and only baseline IL-6 significantly predicted mSASSS week 104 change (β = 0.236, SE = 0.073, p = 0.002, model R 2 = 0.093). By logistic regression, baseline leptin, C3, and tissue inhibitor of metalloproteinase (TIMP)-1 correlated with new fatty lesions per spinal MRI at week 14 and week 104 (both p < 0.01). Changes in serum C3 levels at week 4 (r s = 0.55, p = 0.001) and week 14 (r s = 0.49, p = 0.040) significantly correlated with BASDAI improvement at week 14. Baseline IL-6 and TIMP-1 (r s = −0.63, −0.67; p < 0.05) and reductions at week 4 in IL-6 (r s = 0.61, p < 0.05) and C3 (r s = 0.72; p < 0.05) significantly correlated with week 14 ASspiMRI-a improvement. Conclusions Extensive serum biomarker multiparametric analyses in golimumab-treated patients with ankylosing spondylitis demonstrated few correlations with disease activity or MRI changes; IL-6 weakly correlated with radiographic progression

Long-term efficacy and safety of secukinumab 150 mg in ankylosing spondylitis : 5-year results from the phase III MEASURE 1 extension study

Objective: This study aimed to report end-of-study results on efficacy and safety of secukinumab 150 mg through 5 years in patients with ankylosing spondylitis (AS; MEASURE 1 extension trial (NCT01863732)). Methods: After the 2-year core trial, 274 patients receiving subcutaneous secukinumab 150 or 75 mg (following intravenous loading or initial placebo treatment to 16/24 weeks) every 4 weeks were invited to enter the 3-year extension study. Dose escalation from 75 to 150 mg (approved dose) was allowed at or after week 156 based on the judgement of the treating physician. Assessments at week 260 (5 years) included Assessment of SpondyloArthritis international Society (ASAS) 20/40 and other efficacy outcomes. Data are presented as observed. Safety assessment included all patients who received >= 1 dose of study treatment. Results: Of the 274 patients who entered the extension study, 84% (230/274) completed 5 years of treatment. ASAS20/40 responses were 78.6/65.2%, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 response was 63.4% and mean (+/- SD) BASDAI total score was 2.6 +/- 1.76 with secukinumab 150 mg at 5 years. Improvements in efficacy outcomes were sustained through 5 years. A total of 82 patients on secukinumab 75 mg (56.2%) had their dose escalated to 150 mg after week 168; ASAS40, ASAS-PR, ASAS 5/6 and BASDAI50 responses were improved in patients whose dose was escalated from secukinumab 75 to 150 mg. Secukinumab was well tolerated with a safety profile consistent over the course of the study. Conclusions: Secukinumab 150 mg provided sustained efficacy across multiple domains of AS with a favourable and consistent safety profile through 5-year treatment. Over 50% of patients required dose escalation from 75 to 150 mg and efficacy improved in these patients