Recomendaciones SER sobre el tratamiento del síndrome de Behçet refractario / SER recommendations on treatment of refractory Behçet's syndrome

Objetivo: Elaborar recomendaciones multidisciplinares, basadas en la evidencia disponible y el consenso de expertos, para el manejo terapéutico de los pacientes con síndrome de Behçet refractario (difícil de tratar, resistente grave, recidivante grave) al tratamiento convencional. Métodos: Un panel de expertos identificó preguntas clínicas de investigación relevantes para el objetivo del documento. Estas preguntas fueron reformuladas en formato PICO –paciente, intervención, comparación, outcome o desenlace–. A continuación, se realizaron revisiones sistemáticas; la evaluación de la calidad de la evidencia se realizó siguiendo la metodología del grupo internacional de trabajo Grading of Recommendations, Assessment, Development, and Evaluation. Tras esto, el panel multidisciplinar formuló las recomendaciones. Resultados: Se seleccionaron 4 preguntas PICO relativas a la eficacia y seguridad de los tratamientos farmacológicos sistémicos en los pacientes con síndrome de Behçet con manifestaciones clínicas refractarias a terapia convencional, relacionadas con los fenotipos mucocutáneo y/o articular, vascular, neurológico-parenquimatoso y gastrointestinal. Se formularon un total de 7 recomendaciones estructuradas por pregunta, con base en la evidencia encontrada y el consenso de expertos. Conclusiones: El tratamiento de las manifestaciones clínicas más graves del síndrome de Behçet carece de evidencia científica sólida y no existen documentos de recomendaciones específicas para los pacientes con enfermedad refractaria a la terapia convencional. Con el fin de aportar una respuesta a esta necesidad, se presenta el primer documento de recomendaciones de la Sociedad Española de Reumatología específicas para el abordaje terapéutico de estos pacientes, que servirá de ayuda en la toma de decisiones clínica y la reducción de la variabilidad en la atención.(AU)

Objective: To develop multidisciplinary recommendations based on available evidence and expert consensus for the therapeutic management of patients with refractory Behçet's syndrome (difficult to treat, severe resistant, severe relapse) to conventional treatment. Methods: A group of experts identified clinical research questions relevant to the objective of the document. These questions were reformulated in PICO format –patient, intervention, comparison and outcome–. Systematic reviews of the evidence were conducted; the quality of the evidence was evaluated following the methodology of the international working group Grading of Recommendations, Assessment, Development, and Evaluation. After that, the multidisciplinary panel formulated the specific recommendations. Results: Four PICO questions were selected regarding the efficacy and safety of systemic pharmacological treatments in patients with Behçet's syndrome with clinical manifestations refractory to conventional therapy related to mucocutaneous and/or articular, vascular, neurological parenchymal and gastrointestinal phenotypes. A total of 7 recommendations were made, structured by question, based on the identified evidence and expert consensus. Conclusions: The treatment of most severe clinical manifestations of Behçet's syndrome lacks solid scientific evidence and, besides, there are no specific recommendation documents for patients with refractory disease. With the aim of providing a response to this need, here we present the first official recommendations of the Spanish Society of Rheumatology for the management of these patients. They are devised as a tool for assistance in clinical decision making, therapeutic homogenisation and to reduce variability in the care of these patients.(AU)

SER recommendations on treatment of refractory Behçet's syndrome.

OBJECTIVE: To develop multidisciplinary recommendations based on available evidence and expert consensus for the therapeutic management of patients with refractory Behçet's syndrome (BS) (difficult to treat, severe resistant, severe relapse) to conventional treatment. METHODS: A group of experts identified clinical research questions relevant to the objective of the document. These questions were reformulated in PICO format (patient, intervention, comparison and outcome). Systematic reviews of the evidence were conducted, the quality of the evidence was evaluated following the methodology of the international working group Grading of Recommendations Assessment, Development, and Evaluation (GRADE). After that, the multidisciplinary panel formulated the specific recommendations. RESULTS: 4 PICO questions were selected regarding the efficacy and safety of systemic pharmacological treatments in patients with BS with clinical manifestations refractory to conventional therapy related to mucocutaneous and/or articular, vascular, neurological parenchymal and gastrointestinal phenotypes. A total of 7 recommendations were made, structured by question, based on the identified evidence and expert consensus. CONCLUSIONS: The treatment of most severe clinical manifestations of BS lacks solid scientific evidence and, besides, there are no specific recommendation documents for patients with refractory disease. With the aim of providing a response to this need, here we present the first official Recommendations of the Spanish Society of Rheumatology for the management of these patients. They are devised as a tool for assistance in clinical decision making, therapeutic homogenisation and to reduce variability in the care of these patients.

Incidence and clinical manifestations of giant cell arteritis in Spain: results of the ARTESER register.

OBJECTIVE: This study aimed to estimate the incidence of giant cell arteritis (GCA) in Spain and to analyse its clinical manifestations, and distribution by age group, sex, geographical area and season. METHODS: We included all patients diagnosed with GCA between 1 June 2013 and 29 March 2019 at 26 hospitals of the National Health System. They had to be aged ≥50 years and have at least one positive results in an objective diagnostic test (biopsy or imaging techniques), meet 3/5 of the 1990 American College of Rheumatology classification criteria or have a clinical diagnosis based on the expert opinion of the physician in charge. We calculated incidence rate using Poisson regression and assessed the influence of age, sex, geographical area and season. RESULTS: We identified 1675 cases of GCA with a mean age at diagnosis of 76.9±8.3 years. The annual incidence was estimated at 7.42 (95% CI 6.57 to 8.27) cases of GCA per 100 000 people ≥50 years with a peak for patients aged 80-84 years (23.06 (95% CI 20.89 to 25.4)). The incidence was greater in women (10.06 (95% CI 8.7 to 11.5)) than in men (4.83 (95% CI 3.8 to 5.9)). No significant differences were found between geographical distribution and incidence throughout the year (p=0.125). The phenotypes at diagnosis were cranial in 1091 patients, extracranial in 337 patients and mixed in 170 patients. CONCLUSIONS: This is the first study to estimate the incidence of GCA in Spain at a national level. We found a predominance among women and during the ninth decade of life with no clear variability according to geographical area or seasons of the year.

Subclinical giant cell arteritis in new onset polymyalgia rheumatica A systematic review and meta-analysis of individual patient data.

OBJECTIVES: To determine the prevalence and predictors of subclinical giant cell arteritis (GCA) in patients with newly diagnosed polymyalgia rheumatica (PMR). METHODS: PubMed, Embase, and Web of Science Core Collection were systematically searched (date of last search July 14, 2021) for any published information on any consecutively recruited cohort reporting the prevalence of GCA in steroid-naïve patients with PMR without cranial or ischemic symptoms. We combined prevalences across populations in a random-effect meta-analysis. Potential predictors of subclinical GCA were identified by mixed-effect logistic regression using individual patient data (IPD) from cohorts screened with PET/(CT). RESULTS: We included 13 cohorts with 566 patients from studies published between 1965 to 2020. Subclinical GCA was diagnosed by temporal artery biopsy in three studies, ultrasound in three studies, and PET/(CT) in seven studies. The pooled prevalence of subclinical GCA across all studies was 23% (95% CI 14%-36%, I2=84%) for any screening method and 29% in the studies using PET/(CT) (95% CI 13%-53%, I2=85%) (n=266 patients). For seven cohorts we obtained IPD for 243 patients screened with PET/(CT). Inflammatory back pain (OR 2.73, 1.32-5.64), absence of lower limb pain (OR 2.35, 1.05-5.26), female sex (OR 2.31, 1.17-4.58), temperature >37° (OR 1.83, 0.90-3.71), weight loss (OR 1.83, 0.96-3.51), thrombocyte count (OR 1.51, 1.05-2.18), and haemoglobin level (OR 0.80, 0.64-1.00) were most strongly associated with subclinical GCA in the univariable analysis but not C-reactive protein (OR 1.00, 1.00-1.01) or erythrocyte sedimentation rate (OR 1.01, 1.00-1.02). A prediction model calculated from these variables had an area under the curve of 0.66 (95% CI 0.55-0.75). CONCLUSION: More than a quarter of patients with PMR may have subclinical GCA. The prediction model from the most extensive IPD set has only modest diagnostic accuracy. Hence, a paradigm shift in the assessment of PMR patients in favour of implementing imaging studies should be discussed.

Long-term follow-up of certolizumab pegol in uveitis due to immune-mediated inflammatory diseases: multicentre study of 80 patients.

OBJECTIVES: To evaluate effectiveness and safety of certolizumab pegol (CZP) in uveitis due to immune-mediated inflammatory diseases (IMID). METHODS: Multicentre study of CZP-treated patients with IMID uveitis refractory to conventional immunosuppressant. Effectiveness was assessed through the following ocular parameters: best-corrected visual acuity, anterior chamber cells, vitritis, macular thickness and retinal vasculitis. These variables were compared between the baseline, and first week, first, third, sixth months, first and second year. RESULTS: We studied 80 (33 men/47 women) patients (111 affected eyes) with a mean age of 41.6±11.7 years. The IMID included were: spondyloarthritis (n=43), Behçet's disease (n=10), psoriatic arthritis (n=8), Crohn's disease (n=4), sarcoidosis (n=2), juvenile idiopathic arthritis (n=1), reactive arthritis (n=1), rheumatoid arthritis (n=1), relapsing polychondritis (n=1), CONCLUSIONS: CZP seems to be effective and safe in uveitis related to different IMID, even in patients refractory to previous biological drugs.

Influence of the EULAR recommendations for the use of imaging in large vessel vasculitis in the diagnosis of giant cell arteritis: results of the ARTESER register.

OBJECTIVE: The main study objective was to determine how giant cell arteritis (GCA) is diagnosed in our clinical practice and whether the EULAR recommendations have influenced the diagnostic procedures used. METHODS: ARTEritis of the Rheumatology Spanish Society -Sociedad Española de Reumatología (ARTESER) is a multicentre observational retrospective study conducted in 26 hospitals with support from the Spanish Society of Rheumatology. All patients diagnosed with GCA between 1 June 2013 and 29 March 2019 were included. The gold standard for the diagnosis of GCA was the judgement of the physician in charge, according to clinical criteria, supported by data available from laboratory tests, imaging studies (ultrasound, positron emission tomography (PET) and MRI/CT angiography) and temporal artery biopsy (TAB) when available. RESULTS: We included 1675 patients with GCA (mean age±SD (76.9±8.1) years, 1178 women (70.3%)). Of these, 776 patients had a positive TAB (46.3%), 503 (30.0%) positive ultrasound, 245 positive PET (14.6%) and 64 positive MRI/CT angiography (3.8%). These percentages changed substantially over the study. From 2013 to 2019, the use of ultrasound in diagnosis grew from 25.8% to 52.9% and PET from 12.3% to 19.6%, while use of TAB decreased from 50.3% to 33.3%. CONCLUSIONS: Biopsy was the most widely used diagnostic test for confirming GCA, but use of imaging as a diagnostic tool has grown in recent years. Following publication of the 2018 EULAR recommendations, ultrasound has displaced biopsy as the first-line diagnostic test; TAB was performed in a third and PET in a fifth of cases.

Interobserver reliability of Masei index validation by a multicenter collaborative group of rheumatologists.

MASEI is the main validated ultrasound score for the evaluation of enthesis. The lack of studies facing the agreement to achieve for the interpretation of the MAdrid Sonographic Enthesis Index (MASEI) among researchers from different centers in multicenter studies is of concern. The aim of this multicenter was to evaluate the interobserver reliability of MASEI. An experienced ultrasonographer-rheumatologist performed ultrasound scans of the areas included in MASEI index in three patients with Ankylosing Spondylitis and Psoriatic Arthritis. Videos were captured. The videos were then evaluated by 24 rheumatologists of the ultrasound working group of the Catalan Society of Rheumatology (EcoCAT). A face-to-face training meeting was held. Ten days after the workshop, the study participants evaluated the videos. A reliability assessment was performed. The ICC for the MASEI scores after the workshop was of 0.97 (95% CI 89-99). Reliability did not vary statistically with examiner experience. Globally, no problems of reliability by structures were seen, and all the ICCs were above 0.90 and improved slightly after the educational program. However, the correlation observed between examiners at plantar aponeursis and triceps tendon was weak. The small variability observed in the results of the index validation in our study, suggests that the MASEI index is reproducible by different observers when those are well trained and show awesome results of the enthesis when examined by ultrasound.

"The added value of 18f-FDG PET/CT in the assessment of onset and steroid resistant polimyalgia rheumatica".

PMR is a common inflammatory rheumatic disease. Although its clinical characteristics are fully recognized, no specific test for its diagnosis has been established to date. Several studies have described a wide variety of diseases that present with polymyalgic symptoms. A 18FDG-PET/CT scan could help to deal with these differential diagnoses. The goal of our study is to describe the findings of the 18FDG-PET/CT scan in a cohort of PMR patients and to detail how the 18FDG-PET/CT scan improves accuracy when diagnosing other underlying conditions. This cross-sectional study enrolled patients with a diagnosis of PMR who underwent to a 18FDG-PET/CT scan to rule out other diagnosis. The 18FDG-PET/CT scan was performed either following clinical criteria at the onset of clinical symptoms or when the patient became PMR steroid resistant. Patients' demographic, clinical and analytical data at the moment of the 18FDG-PET/CT scan were recorded. The final diagnosis was confirmed according to clinical judgement. A total of 103 patients with PMR were included. In 49.51% of patients, the 18FDG-PET/CT scan was ordered to study resistance to steroid therapy. The final diagnoses of patients were PMR in 70.9% patients, large vessel vasculitis in 15.5%, neoplasms 4.8% and another diagnosis in the rest. The 18FDG-PET/CT scan is a very useful technique for the study of Polymyalgia Rheumatica, not only to help in the diagnostic process, but also due to its role in the identification of a variety of PMR-like patrons.

Interstitial Lung Disease and Anti-Myeloperoxidase Antibodies: Not a Simple Association.

Anti-neutrophil cytoplasmic antibodies (ANCA), mainly anti-myeloperoxidase (MPO) antibodies, have been frequently identified in patients with idiopathic pulmonary fibrosis (IPF). However, their role remains unclear, and only 7-23% of these patients develops clinically overt vasculitis. We aimed to investigate the clinical, serological, and radiological features and prognosis of anti-MPO-positive interstitial lung disease (ILD) patients. Fifty-eight consecutive patients firstly referred for idiopathic interstitial pneumonia and showing serological positivity of anti-MPO antibodies were retrospectively enrolled. For each patient, clinical data, lung function testing, chest high-resolution computed tomography (HRCT) pattern, and survival were recorded. Thirteen patients developed a rheumatic disease during a median follow-up of 39 months. Usual interstitial pneumonia (UIP) was the most frequent ILD pattern, significantly influencing the patients' survival. In fact, while the 52-week survival of the overall population was 71.4 ± 7.5%, significantly higher than IPF, survivals of anti-MPO patients with UIP pattern and IPF were similar. Forced vital capacity and diffusion lung capacity for CO significantly declined in 37.7 and 41.5% of cases, respectively, while disease progression at chest HRCT was observed in 45.2%. A careful clinical history and evaluation should always be performed in ILD patients with anti-MPO antibodies to quickly identify patients who are developing a systemic rheumatic disease.

Vacunación antigripal y antineumocócica 23 valencias en pacientes reumáticos en tratamiento con inmunosupresores / Influenza and pneumococcal (23-valent) vaccination in rheumatic patients on treatment with immunosuppressants

Objetivo: determinar la evolución de la tasa de vacunación antigripal y antineumocócica (23 valencias) entre los años 2010 y 2014 en pacientes reumáticos en tratamiento con inmunosupresores y evaluar la magnitud de infecciones respiratorias documentadas en el año posterior a la vacunación. Método: estudio descriptivo longitudinal retrospectivo. Se reclutaron por conveniencia 200 pacientes con artritis reumatoide o espondiloartropatías en tratamiento con fármacos antirreumáticos modificadores de la enfermedad (FAME) sintético, FAME biológico o corticoides. Se conformaron dos grupos de 100 pacientes (2010 y 2014) en los que se revisaron historias clínicas para recoger variables demográficas, comorbilidades, hábitos tóxicos, diagnóstico reumatológico y años de evolución de este, tratamiento, administración de la vacuna antigripal y antineumocócica 23v y número de infecciones respiratorias en el año posterior. Resultados: en la muestra un 66% fue mujer, la edad media fue de 66 años y 12 de evolución de la enfermedad. El 43,5% había recibido vacunación antigripal y el 30% vacunación neumocócica 23v. El 21,5% presentó infección respiratoria en el tiempo de seguimiento. Hubo una mayor tasa de vacunación antigripal y antineumocócica en 2014 frente a 2010 (49 y 29% vs. 38% y 21%, respectivamente), siendo solo estadísticamente significativo el aumento en la cobertura antineumocócica. Los pacientes mayores de 65 años y alguna comorbilidad o hábito tóxico son más vacunados (p< 0,05). No hubo diferencias en las vacunaciones ni en el número de infecciones respiratorias, ni en función del diagnóstico reumatológico, ni del tratamiento recibido por el paciente. Conclusiones: la tasa de vacunación mejoró en 2014 respecto a 2010. No obstante, el profesional enfermero ha de intervenir en mejorar la tasa de vacunación en estos pacientes

Objective: to determine the evolution in the rate of influenza and pneumococcal (23-valent) vaccination between the years 2010 and 2014 in rheumatic patients on treatment with immunosuppressants, and to evaluate the extent of documented respiratory infections within the year after vaccination. Method: a retrospective cross-sectional descriptive study. Two hundred (200) patients were recruited by convenience sampling, with rheumatoid arthritis or spondyloarthropathy, on treatment with synthetic disease modifying antirheumatic drugs (DMARDs), biologic DMARDs or corticosteroids. Two arms of 100 patients were formed (2010 and 2014), and clinical records were reviewed in order to collect demographical variables, comorbidities, toxic habits, rheumatology diagnosis and years of disease evolution, treatment, administration of the influenza and the pneumococcal 23 vaccine, and number of respiratory infections during the following year. Results: in the sample, 66% were women, their mean age was 66 years, with 12 years of disease evolution; 43.5% had received influenza vaccination, and 30% pneumococcal 23v vaccination; 21.5% presented respiratory infection within the time of follow-up. There was a higher rate of influenza and pneumococcal vaccination in 2014 vs. 2010 (49 and 29% vs. 38% and 21%, respectively); only the increase in pneumococcal coverage was statistically significant. Patients >65-year-old and with some comorbidity or toxic habit were more vaccinated (p< 0.05). There were no differences in vaccinations or in the number of respiratory infections based on the rheumatology diagnosis or the treatment received by the patient. Conclusions: the vaccination rate improved in 2014 vs. 2010. However, the nursing professional must be involved in the improvement of the vaccination rate for these patients

¿Es rentable la utilización del DAS en el seguimiento clínico de los pacientes con artritis reumatoide? / Is DAS a profitable score to be used for rheumatoid arthritis patient follow up?

La artritis reumatoide (AR) es una enfermedad sistémica inflamatoria articular compleja de diferente presentación y evolución. Una evaluación válida, fiable, sensible y diferenciadora de la actividad inflamatoria es esencial en la práctica clínica para tomar decisiones terapéuticas y valorar la respuesta al tratamiento. Los métodos empleados actualmente para evaluar la actividad de la AR son una combinación de parámetros clínicos, de laboratorio e indicadores de la actividad de la enfermedad, como los criterios del American College of Rheumatology (ACR), el Disease Activity Score (DAS) y el Simplified Disease Activity Index (SDAI). La aparición de nuevas terapias más eficaces, nos obliga a ser más exigentes en nuestros objetivos terapéuticos y por tanto, a plantearnos la rentabilidad de los métodos que utilizamos para el seguimiento de nuestros pacientes (AU)

Rheumatoid Arthritis (RA) is a complex systemic joint inflammatory disease with differing manifestations and evolution. A valid, reliable and sensitive assessment procedure that is able to differentiate the inflammatory activity is essential in clinical practice, both in terms of reaching therapeutic decisions and assessing the response to treatment. The methods currently employed to assess the activity of RA are a combination of clinical parameters, laboratory tests and indicators of the progression of the disease, such as the criteria of the American College of Rheumatology (ACR), the Disease Activity Score (DAS) and the Simplified Disease Activity Index (SDAI). The emergence of new and more effective therapies obliges us to be more demanding in our therapeutic objectives, and therefore to consider the suitability of the methods that we use to follow our patients’ progress (AU)

[Is DAS a profitable score to be used for rheumatoid arthritis patient follow up?]. / Es rentable la utilización del DAS en el seguimiento clínico de los pacientes con artritis reumatoide?

Rheumatoid Arthritis (RA) is a complex systemic joint inflammatory disease with differing manifestations and evolution. A valid, reliable and sensitive assessment procedure that is able to differentiate the inflammatory activity is essential in clinical practice, both in terms of reaching therapeutic decisions and assessing the response to treatment. The methods currently employed to assess the activity of RA are a combination of clinical parameters, laboratory tests and indicators of the progression of the disease, such as the criteria of the American College of Rheumatology (ACR), the Disease Activity Score (DAS) and the Simplified Disease Activity Index (SDAI). The emergence of new and more effective therapies obliges us to be more demanding in our therapeutic objectives, and therefore to consider the suitability of the methods that we use to follow our patients' progress.