Tasas de promoción, repitencia y abandono en la Carrera de Especialistas en Reumatología en la Ciudad de Buenos Aires / Specialty training in rheumatology: Promotion, repetition and dropout rates in the city of Buenos Aires

Objetivos: Evaluar la trayectoria de los alumnos de la Carrera de Especialistas en Reumatología y determinar factores asociados al resultado en el posgrado. Métodos: Análisis retrospectivo (2009-2016). Se determinaron las tasas de promoción, la repitencia y el abandono. Se realizaron análisis multivariados para determinar variables asociadas al éxito académico. Resultados: Sobre 119 alumnos, la promoción efectiva fue del 66,4%, la repitencia sin retraso fue del 14,3%, la repitencia con retraso fue del 11,8% y el abandono fue del 7,6%. La promoción efectiva de la residencia fue del 82,5% vs el 48,2% en el resto (p<0,001), la repitencia con retraso fue del 3,2% vs el 21,4% en el resto (p=0,005) y el abandono fue del 3,2% vs el 12,5% en el resto (p=0,06). El éxito en el posgrado fue mayor a mejor promedio en la carrera de Medicina (OR: 3,41; IC95%: 2,0-6,4; p<0,001). Conclusiones: La residencia se asoció a mayor éxito académico en el posgrado. El puntaje promedio en la cursada de Medicina puede ayudar a identificar a los alumnos en riesgo de fallar.(AU)

Objectives: To evaluate the trajectory of students enrolled in the specialty training in rheumatology. Methods: Retrospective analysis (2009-2016). Promotion, repetition, and dropout rates were determined. Analysis was performed to define variables associated with academic success. Results: Out of 119 students, the actual promotion rate was 66.4%, 11.8% failed an exam (at least) and completed the course after the stipulated time, and the dropout rate was 7.6%. Among residents, the promotion rate was 82.5% vs. 48.2% among the rest (P<.001), the lagging students’ repetition rate was 3.2% vs. 21.4% among the rest (P=.005), and the dropout rate was 3.2% vs. 12.5% among the rest (P=.06). A higher average score in medical school increased the chances of success in the postgraduate programme (OR: 3.41; 95%CI: 2.0-6.4; P<.001). Conclusions: The residency was associated with higher rates of academic success in postgraduate studies. The average score in medical school can help identify students at risk of failure.(AU)

Speciality training in rheumatology: Promotion, repetition and dropout rates in the city of Buenos Aires.

OBJECTIVES: To evaluate the trajectory of students enrolled in the specialty training in rheumatology. METHODS: Retrospective analysis (2009-2016). Promotion, repetition, and dropout rates were determined. Analysis was performed to define variables associated with academic success. RESULTS: Out of 119 students, the actual promotion rate was 66.4%, 11.8% failed an exam (at least) and completed the course after the stipulated time, and the dropout rate was 7.6%. Among residents, the promotion rate was 82.5% vs. 48.2% among the rest (p < 0.001), the lagging students' repetition rate was 3.2% vs. 21.4% among the rest (p 0.005), and the dropout rate was 3.2% vs. 12.5% among the rest (p = 0.06). A higher average score in medical school increased the chances of success in the postgraduate programme (OR 3.41 CI 95% 2.0-6.4; p < 0.001). CONCLUSIONS: The residency was associated with higher rates of academic success in postgraduate studies. The average score in medical school can help identify students at risk of failure.

Seguridad de las drogas biológicas y sintéticas dirigidas utilizadas en pacientes con enfermedades reumáticas inmunomediadas. Datos del registro BIOBADASAR 3.0 / Safety of biological and targeted synthetic drugs in patients with immune-mediated rheumatic diseases. Data from the BIOBADASAR 3.0 registry

Introducción: conocer la seguridad de las drogas actualmente disponibles para el tratamiento de las enfermedades reumáticas es muy importante al momento de tomar decisiones terapéuticas objetivas e individualizadas en la consulta médica diaria. Asimismo, datos de la vida real amplían el conocimiento revelado por los ensayos clínicos. Objetivos: describir los eventos adversos (EA) reportados, estimar su frecuencia e identificar los factores relacionados con su desarrollo. Materiales y métodos: se utilizaron datos BIOBADASAR, un registro voluntario y prospectivo de seguimiento de EA de tratamientos biológicos y sintéticos dirigidos en pacientes con enfermedades reumáticas inmunomediadas. Los pacientes son seguidos hasta la muerte, pérdida de seguimiento o retiro del consentimiento informado. Para este análisis se extrajeron datos recopilados hasta el 31 de enero de 2023. Resultados: se incluyó un total de 6253 pacientes, los cuales aportaron 9533 ciclos de tratamiento, incluyendo 3647 (38,3%) ciclos sin drogas modificadoras de la enfermedad biológicas y sintéticas dirigidas (DME-b/sd) y 5886 (61,7%) con DME-b/sd. Dentro de estos últimos, los más utilizados fueron los inhibidores de TNF y abatacept. Se reportaron 5890 EA en un total de 2701 tratamientos (844 y 1857 sin y con DME-b/sd, respectivamente), con una incidencia de 53,9 eventos cada 1000 pacientes/año (IC 95% 51,9-55,9). La misma fue mayor en los ciclos con DME-b/sd (71,1 eventos cada 1000 pacientes/año, IC 95% 70,7-77,5 versus 33,7, IC 95% 31,5-36,1; p<0,001). Las infecciones, particularmente las de la vía aérea superior, fueron los EA más frecuentes en ambos grupos. El 10,9% fue serio y el 1,1% provocó la muerte del paciente. El 18,7% de los ciclos con DME-b/sd fue discontinuado a causa de un EA significativamente mayor a lo reportado en el otro grupo (11,5%; p<0,001). En el análisis ajustado, las DME-b/sd se asociaron a mayor riesgo de presentar al menos un EA (HR 1,82, IC 95% 1,64-1,96). De igual manera, la mayor edad, el mayor tiempo de evolución, el antecedente de enfermedad pulmonar obstructiva crónica, el diagnóstico de lupus eritematoso sistémico y el uso de corticoides se asociaron a mayor riesgo de EA. Conclusiones: la incidencia de EA fue significativamente superior durante los ciclos de tratamientos que incluían DME-b/sd.

Introduction: knowing the efficacy and safety of the drugs currently available for the treatment of rheumatic diseases is very important when making objective and individualized therapeutic decisions in daily medical consultation. Likewise, real-life data extends the knowledge revealed by clinical trials. Objectives: to describe the reported adverse events (AEs), estimate their frequency and identify factors associated to them. Materials and methods: BIOBADASAR data were used, which is a voluntary, prospective follow-up registry of AEs of biological and synthetic treatments in patients with immune-mediated rheumatic diseases. Patients are followed until death, loss of followup, or withdrawal of informed consent. To carry out this analysis, the data collected up to January 31, 2023 was extracted. Results: a total of 6253 patients were included, who contributed with 9533 treatment periods, including 3647 (38.3%) periods without b/ts-DMARDs and 5886 (61.7%) with b/ts-DMARDs. Among the latter, the most used were TNF inhibitors and abatacept. A total of 5890 AEs were reported in a total of 2701 treatments (844 and 1857 without and with b/ts-DMARDs, respectively), with an incidence of 53.9 events per 1000 patients/ year (95% CI 51.9-55.9). It was higher during the periods with b/ts-DMARDs (71.1 events per 1000 patients/year, 95% CI 70.7-77.5 vs 33.7, 95% CI 31.5-36.1, p<0.001). Infections, particularly those of the upper respiratory tract, were the most frequent AEs in both groups. 10.9% were severe and 1.1% were associated with the death of the patient. 18.7% of the periods with b/ts-DMARDs were discontinued due to an AE, significantly higher than that reported in the other group (11.5%; p<0.001). In the adjusted analysis, b/ts-DMARDs were associated with a higher risk of presenting at least one AE (HR 1.82, 95% CI 1.64-1.96). Similarly, older age, longer evolution time, history of chronic obstructive pulmonary disease, diagnosis of systemic lupus erythematosus, and use of corticosteroids were associated with a higher risk of AE. Conclusions: the incidence of AEs was significantly higher during those treatment periods that included DME-b/sd.

Penfigoide ocular cicatricial: ¿metotrexato como tratamiento de inicio? / Ocular Cicatricial Pemphigoid: Methotrexate as an Initial Treatment?

Objetivo: Analizar los datos clínicos/epidemiológicos, el manejo y los tratamientos instaurados a pacientes con penfigoide ocular cicatricial en un Servicio de Reumatología. Material y métodos: Revisión de historias clínicas de pacientes con penfigoide ocular cicatricial derivados por oftalmología entre 2008 y 2019. Resultados: En nuestra serie de 27 pacientes, el 67% fue diagnosticado y derivado en los últimos 2 años. La mayoría en estadio 1 de Foster. El 18,5% presentó síndrome de Sjogren asociado, conllevando una evolución desfavorable. El 88,8% recibió metotrexato, el 74% lo utilizó en monoterapia y el 66% continuó el tratamiento hasta el final. El 18,5% debió combinar/rotar terapias, los fármacos utilizados fueron micofenolato, azatioprina, ciclofosfamida, sirolimus, rituximab. El 29% utilizó esteroides. Solo en 2 ojos progresó el estadio. No se registraron eventos adversos serios y el 37% presentó eventos adversos leves. Conclusión: El inicio temprano de la terapia inmunosupresora es fundamental, siendo el metotrexato una buena alternativa como tratamiento de inicio según nuestra experiencia, debiendo escalar el tratamiento de acuerdo a la evolución.(AU)

Objective: To analyse the clinical / epidemiological data, the management and the treatments established in patients with ocular cicatricial pemphigoid in a Rheumatology Service. Material and methods: Review of clinical histories of patients with ocular cicatricial pemphigoid referred by ophthalmology between 2008 and 2019. Results: In our series of 27 patients, 67% were diagnosed and referred in the last 2 years. Most in Foster stage 1. Of the patients, 18.5% presented associated Sjogren's syndrome, with poor progression: 88.8% received Methotrexate, 74% used it as monotherapy and 66% continued with said treatment up to the end. Eighteen point five percent had to combine or rotate therapies, the drugs used were mycophenolate, azathioprine, cyclophosphamide, sirolimus, etanercept, rituximab: 29% used steroids. Only in 2 eyes was stage progression observed. There were no serious adverse events, and 37% had mild adverse events. Conclusion: Starting immunosuppressive therapy early is essential, methotrexate being a good initial alternative in our experience, and treatment must be escalated in line with disease progression.(AU)

Ocular cicatricial pemphigoid: Methotrexate as an initial treatment?

OBJECTIVE: To analyse the clinical/epidemiological data, the management and the treatments established in patients with Ocular Cicatricial Pemphigoid (OCP) in a Rheumatology Service. MATERIAL AND METHODS: Review of clinical histories of patients with OCP referred by ophthalmology between 2008 and 2019. RESULTS: In our series of 27 patients, 67% were diagnosed and referred in the last 2 years. Most in Foster stage 1. Of the patients, 18.5% presented associated Sjogren's syndrome, with poor progression: 88.8% received Methotrexate, 74% used it as monotherapy and 66% continued with said treatment up to the end. Eighteen point five percent had to combine or rotate therapies, the drugs used were mycophenolate, azathioprine, cyclophosphamide, sirolimus, etanercept, rituximab: 29% used steroids. Only in 2 eyes was stage progression observed. There were no serious adverse events, and 37% had mild adverse events. CONCLUSION: Starting immunosuppressive therapy early is essential, methotrexate being a good initial alternative in our experience, and treatment must be escalated in line with disease progression.

Collaborative registry of pulmonary hypertension in Argentina (RECOPILAR). Final analysis / Registro colaborativo de hipertensión pulmonar en Argentina (RECOPILAR): análisis final

Abstract The epidemiology of pulmonary hypertension (PH), especially pulmonary arterial hypertension (PAH), has not been evaluated in our country, therefore there is no reference parameter to establishing the representativeness of this information in the national order. This registry represents the first collaborative effort to provide a knowledge base of this disease, including 5 scientific societies that represent different specialties (pediatrics, rheumatology, pulmonology and cardiology) with data from 23 Argentine provinces. These efforts involved five societies of various adult (cardiology, rheumatology, and pulmonology) and pediatric (cardiology) specialties. Subjects were grouped (1-5) in accord with the 2013 Nice classification. A total of 627 patients (mean age, 50.8±18 years; women, 69.2%) were recruited. Incident cases accounted for 53%. Functional class III-IV accounted for 69% at time of diagnosis and 33.4% at time of inclusion. Distributions in groups 1-5 were 63.6%, 15.9%, 8.3%, 9.7%, and 2.4%, respectively. Treatment consisted of diuretics (51.2%), mineralocorticoid receptor antagonists (44.7%), digoxin (16.6%), anticoagulants (39.2%), renin-angiotensin antagonists (15.5%), beta blockers (15.6%), and calcium channel blockers (8%). Rates of specific therapies usage in PAH vs. non-PAH group were 80.5% vs. 40.8% (phosphodiesterase-5 inhibitors: 71% vs. 38.6%; endothelin receptor antagonists: 54.4% vs. 14.5%; prostanoids: 14.3 vs. 3.1%; all p < 0.001). Three-year survival in PAH and non-PAH differed significantly (82.8% vs. 73.3%; p = 0.001). In the Argentine RECOPILAR registry, the clinic-epidemiologic profile was that of advanced-stage disease. Diagnostic workups and therapeutics interventions, including use of specific therapy for PAH, were consistent with current recommendations. Despite delays in diagnosis, survival was aligned with other contemporary registries.

Resumen La epidemiología de la hipertensión pulmonar (HP), especialmente la arterial (HAP), no ha sido evaluada en nuestro país, por lo cual no existe un parámetro de referencia para establecer la representatividad de esta información en el orden nacional. El presente registro representa el primer esfuerzo colaborativo para una base de conocimiento de esta enfermedad, incluyendo 5 sociedades científicas que representan a distintas especiali dades médicas (pediatría, reumatología, neumonología y cardiología) con datos de 23 provincias argentinas. Los sujetos se agruparon (1-5) de acuerdo con la clasificación de Niza de 2013. El seguimiento se completó en 583 pacientes (93%) un año después del final de la inscripción. Se incluyeron 627 pacientes (edad media, 50.8 ± 18 años; mujeres, 69.2%). Los casos incidentes representaron el 53%. La clase funcional III-IV representaba 69% en el momento del diagnóstico y 33.4% en el momento de la inclusión. Las manifestaciones clínicas fueron disnea (81.8%), fatiga (54.1%), síncope (10.8%), dolor torácico (14.7%), palpitaciones (20.9%) e insuficiencia cardíaca (20.4%). Las tasas de uso de terapias específicas en la hipertensión arterial pulmonar (HAP) frente al grupo sin HAP fueron del 80.5% frente al 40.8%. La supervivencia a tres años en los subconjuntos de HAP y no HAP difirió significativamente (82.8% vs. 73.3%; p = 0.001). En el registro RECOPILAR argentino, que aborda principalmente la HAP, el perfil clínico-epidemiológico fue el d e una enfermedad en estadios avanzados. El diag nóstico y las intervenciones terapéuticas, incluido el uso de terapia específica para la HAP, fueron consistentes con las recomendaciones actuales.

Collaborative registry of pulmonary hypertension in Argentina (RECOPILAR). Final analysis.

The epidemiology of pulmonary hypertension (PH), especially pulmonary arterial hypertension (PAH), has not been evaluated in our country, therefore there is no reference parameter to establishing the representativeness of this information in the national order. This registry represents the first collaborative effort to provide a knowledge base of this disease, including 5 scientific societies that represent different specialties (pediatrics, rheumatology, pulmonology and cardiology) with data from 23 Argentine provinces. These efforts involved five societies of various adult (cardiology, rheumatology, and pulmonology) and pediatric (cardiology) specialties. Subjects were grouped (1-5) in accord with the 2013 Nice classification. A total of 627 patients (mean age, 50.8 ± 18 years; women, 69.2%) were recruited. Incident cases accounted for 53%. Functional class III-IV accounted for 69% at time of diagnosis and 33.4% at time of inclusion. Distributions in groups 1-5 were 63.6%, 15.9%, 8.3%, 9.7%, and 2.4%, respectively. Treatment consisted of diuretics (51.2%), mineralocorticoid receptor antagonists (44.7%), digoxin (16.6%), anticoagulants (39.2%), renin-angiotensin antagonists (15.5%), beta blockers (15.6%), and calcium channel blockers (8%). Rates of specific therapies usage in PAH vs. non-PAH group were 80.5% vs. 40.8% (phosphodiesterase-5 inhibitors: 71% vs. 38.6%; endothelin receptor antagonists: 54.4% vs. 14.5%; prostanoids: 14.3 vs. 3.1%; all p < 0.001). Three-year survival in PAH and non-PAH differed significantly (82.8% vs. 73.3%; p = 0.001). In the Argentine RECOPILAR registry, the clinic-epidemiologic profile was that of advanced-stage disease. Diagnostic workups and therapeutics interventions, including use of specific therapy for PAH, were consistent with current recommendations. Despite delays in diagnosis, survival was aligned with other contemporary registries.

La epidemiología de la hipertensión pulmonar (HP), especialmente la arterial (HAP), no ha sido evaluada en nuestro país, por lo cual no existe un parámetro de referencia para establecer la representatividad de esta información en el orden nacional. El presente registro representa el primer esfuerzo colaborativo para una base de conocimiento de esta enfermedad, incluyendo 5 sociedades científicas que representan a distintas especialidades médicas (pediatría, reumatología, neumonología y cardiología) con datos de 23 provincias argentinas. Los sujetos se agruparon (1-5) de acuerdo con la clasificación de Niza de 2013. El seguimiento se completó en 583 pacientes (93%) un año después del final de la inscripción. Se incluyeron 627 pacientes (edad media, 50.8 ± 18 años; mujeres, 69.2%). Los casos incidentes representaron el 53%. La clase funcional III-IV representaba 69% en el momento del diagnóstico y 33.4% en el momento de la inclusión. Las manifestaciones clínicas fueron disnea (81.8%), fatiga (54.1%), síncope (10.8%), dolor torácico (14.7%), palpitaciones (20.9%) e insuficiencia cardíaca (20.4%). Las tasas de uso de terapias específicas en la hipertensión arterial pulmonar (HAP) frente al grupo sin HAP fueron del 80.5% frente al 40.8%. La supervivencia a tres años en los subconjuntos de HAP y no HAP difirió significativamente (82.8% vs. 73.3%; p = 0.001). En el registro RECOPILAR argentino, que aborda principalmente la HAP, el perfil clínico-epidemiológico fue el d e una enfermedad en estadios avanzados. El diagnóstico y las intervenciones terapéuticas, incluido el uso de terapia específica para la HAP, fueron consistentes con las recomendaciones actuales.

Ocular Cicatricial Pemphigoid: Methotrexate as an Initial Treatment? / Penfigoide ocular cicatricial: ¿metotrexato como tratamiento de inicio?

OBJECTIVE: To analyse the clinical / epidemiological data, the management and the treatments established in patients with ocular cicatricial pemphigoid in a Rheumatology Service. MATERIAL AND METHODS: Review of clinical histories of patients with ocular cicatricial pemphigoid referred by ophthalmology between 2008 and 2019. RESULTS: In our series of 27 patients, 67% were diagnosed and referred in the last 2 years. Most in Foster stage 1. Of the patients, 18.5% presented associated Sjogren's syndrome, with poor progression: 88.8% received Methotrexate, 74% used it as monotherapy and 66% continued with said treatment up to the end. Eighteen point five percent had to combine or rotate therapies, the drugs used were mycophenolate, azathioprine, cyclophosphamide, sirolimus, etanercept, rituximab: 29% used steroids. Only in 2 eyes was stage progression observed. There were no serious adverse events, and 37% had mild adverse events. CONCLUSION: Starting immunosuppressive therapy early is essential, methotrexate being a good initial alternative in our experience, and treatment must be escalated in line with disease progression.

Performance of the RABBIT infection risk score in an Argentinian rheumatoid arthritis cohort.

Patients with rheumatic autoimmune diseases have a higher risk of infections compared with age-and sex-matched controls. In Latin America, there are no validated tools to assess the risk of serious infection. The objectives were to estimate the incidence of serious infections in a cohort of rheumatoid arthritis (RA) patients followed for 12 months and to validate the RABBIT risk score for serious infections. Patients with RA were included and followed for 12 months. Baseline sociodemographic data, comorbidities, RA characteristics, and vaccination status were recorded. The baseline RABBIT risk score was calculated. Serious infections were documented, describing site and time since enrollment. Six hundred five patients were included (13 centers). The incidence of serious infection was 5% (95% CI 3-7). The most frequent sites were respiratory and urinary (90%). Performance of RABBIT risk score: patients with no infection during follow-up had a median score of 1.2 (IQR 0.8-2.1) and patients with infection 5.1 (IQR 2.15-12.6) p 0.00001. ROC curve analysis: AUC 0.86 (95% CI 0.8-0.94), best cut-off 2.85 (sensibility 75%, specificity 85%). The incidence of serious infections was 5% during the follow-up. The RABBIT score performed excellently in our patients. Key Points • The RABBIT risk score for serious infections showed an excellent performance in a population different (Latin America) from the original one included in the German registry. • This may assist rheumatologists in selecting drugs for patients according to the individual risk of infection, in a fast and simple way.

Asociación entre Artritis Reumatoidea y otras enfermedades autoinmunes / Association between Rheumatoid Arthritis and other autoimmune diseases

Objetivos: Determinar la frecuencia de enfermedades autoinmunes (EAI) en pacientes con Artritis Reumatoidea (AR) y comparar la frecuencia de EAI entre pacientes con AR y sin AR ni otra EAI reumatológica. Material y Métodos: Estudio multicéntrico, observacional, analítico, retrospectivo. Se incluyeron pacientes consecutivos con AR (ACR/EULAR 2010) y como grupo control pacientes con diagnóstico inicial de Osteoartritis primaria (OA). Resultados: Se incluyeron 1549 pacientes: 831 con AR (84% mujeres, edad media 55.2 años [DE 13.6]) y 718 con OA (82% mujeres, edad media 67 años [DE 11.1]). La frecuencia de EAI en el grupo AR fue del 22% (n=183). Estos presentaron mayor frecuencia de EAI reumatológicas (9.4 vs 3.3%, p< 0.001), y menor frecuencia de EAI no reumatológicas que aquellos con OA (15.3 vs 20.5, p=0.007). La EAI reumatológica más prevalente fue el Síndrome de Sjögren, el cual fue más frecuente en el grupo AR (87.2 vs 29.2%, p< 0,001). La frecuencia de EAI reumatológicas en los pacientes con AR fue mayor en la forma erosiva (11 vs 6.8%, p=0.048). Conclusión: La frecuencia de EAI en los pacientes con AR fue del 22%, en quienes predominaron las de etiología reumatológica mientras que, las no reumatológicas predominaron en pacientes con OA.

Objectives: To determine the frequency of autoimmune diseases (AID) in Rheumatoid Arthritis (RA) patients and to compare this frequency between patients with and without RA or other rheumatologic AID. Methods: Multicenter, observational, analytical, retrospective study. Consecutive patients with diagnosis of RA (ACR/EULAR 2010) were included. Patients with initial diagnosis of primary ostearthritis (OA) were used as control group. Results: A total of 1549 patients were included: 831 RA (84% women, mean age 55.2 [±13.6]) and 718 OA (82% women, mean age 67 [± 11.1]). The frequency of AID in the RA group was 22% (n=183). RA patients showed higher frequency of rheumatologic AID (9.4 vs 3.3%, p< 0.001), and lower frequency of non-rheumatologic AID than OA patients (15.3 vs 20.5%, p= 0.007). The most prevalent rheumatic AID was Sjögren's Syndrome, which was more frequent in the AR group (87.2 vs 29.2%, p<0.001). The frequency of rheumatologic AID in RA patients was higher in those with erosive RA (11 vs 6.8%, p=0.048). Conclusion: The frequency of AID in RA patients was 22%. Rheumatologic AID were more frequent in RA patients, whereas non-rheumatologic AID prevailed in OA patients.

Changing rate of serious infections in biologic-exposed rheumatoid arthritis patients. Data from South American registries BIOBADABRASIL and BIOBADASAR.

OBJECTIVE: Most reports on serious infections (SI) in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) are from the USA and Western Europe. Data from other regions are largely missing. We report data from South American countries with different backgrounds and health-care systems but similar registries. METHODS: We merged 2010-2016 data from two registries, BIOBADABRASIL (Brazil) and BIOBADASAR (Argentina), which share the same protocol, online platform and data monitoring process. Patients with active RA were included when they began the first bDMARD or a conventional synthetic DMARD (csDMARD, control group). The SI incidence rate (IR) per 1000 patient/years and adjusted IR ratio (aIRR) were estimated for bDMARDs and csDMARDs. RESULTS: Data were analysed for 3717 RA patients with an exposure of 13,380 patient/years. The 2591 patients treated with bDMARDs (64% tumour necrosis factor-α inhibitors (TNFi)) had a follow-up of 9300 years, and the 1126 treated with csDMARDs had an exposure of 4081 patient/years. The SI IR was 30.54 (CI 27.18-34.30) for all bDMARDs and 5.15 (CI 3.36-7.89) for csDMARDs. The aIRR between the two groups was 2.03 ([1.05, 3.9] p = 0.034) for the first 6 months of treatment but subsequently increased to 8.26 ([4.32, 15.76] p < 0.001). The SI IR for bDMARDs decreased over time in both registries, dropping from 36.59 (28.41-47.12) in 2012 to 7.27 (4.79-11.05) in 2016. CONCLUSION: While SI remains a major concern in South American patients with RA treated with bDMARDs, a favourable trend toward a reduction was observed in the last years.Key Points• New comprehensive data on biologic drugs safety from international collaboration in South America.• First proposal for national registries data merging in South America.• Serious infections remain a major concern in RA patients treated with biologics.• A significant reduction of serious infections in RA patients exposed to biologics was observed over a 7 years period.

Tocilizumab Patterns of Use, Effectiveness, and Safety in Patients with Rheumatoid Arthritis: Final Results from a Set of Multi-National Non-Interventional Studies.

INTRODUCTION: The objective of this study was to observe the patterns of usage, efficacy, and safety of tocilizumab (TCZ) in clinical practice in patients with rheumatoid arthritis. METHODS: Data on the real-world usage, efficacy, and safety of TCZ were collected from patients during routine follow-up visits conducted over a 6-month period. Patients were grouped by previous exposure to biologic therapies (biologic exposed vs. biologic naive). RESULTS: Of 1912 patients enrolled from 16 countries, 639 (33.4%) received TCZ monotherapy and 1273 (66.6%) received TCZ combination therapy. At baseline, 1073 patients (56.1%) were biologic naive and 839 (43.9%) were biologic exposed. At 6 months, 1504 patients (78.7%) continued to receive TCZ treatment, with no descriptive differences in retention rates between biologic-exposed and biologic-naive patients and between patients receiving TCZ monotherapy or combination therapy. Dose and use of methotrexate and prednisone were reduced at 6 months. Efficacy at 6 months, including patient-reported outcomes, was demonstrated in both biologic-naive and biologic-exposed groups. Adverse events (AEs) occurred in 817 patients [42.7%; incidence rate: 179 events per 100 patient-years (PY)], and serious AEs (SAEs) occurred in 118 patients (6.2%; 17 events per 100 PY), with comparable rates of AEs and SAEs between subgroups. CONCLUSION: In routine clinical practice, TCZ discontinuation rates were low and unaffected by prior use of biologics. Effectiveness was similar between groups, and no new safety signals were identified. FUNDING: F. Hoffmann-La Roche.

Patterns of tocilizumab use, effectiveness and safety in patients with rheumatoid arthritis: core data results from a set of multinational observational studies.

OBJECTIVES: To observe patients with rheumatoid arthritis (RA) treated with the interleukin-6 receptor-alpha inhibitor tocilizumab (TCZ) in routine clinical practice. METHODS: Data on concomitant medications, effectiveness and safety were pooled from independent, multinational studies in patients with RA initiating intravenous TCZ according to local label recommendations observed in routine practice for 6 months. Patients were grouped by TCZ monotherapy or combination therapy with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). The primary endpoint was the proportion of patients receiving TCZ after 6 months. RESULTS: Of 1336 patients enrolled, 506 (37.9%) received TCZ monotherapy and 830 (62.1%) received combination therapy. Kaplan-Meier analysis estimated that 80% (95% CI, 76%-83%) of monotherapy and 87% (95% CI, 84%-89%) of combination therapy patients continued to receive TCZ at 6 months (log-rank p<0.001). During the observation period, TCZ was discontinued by 113 (22.3%) monotherapy patients and 116 (14.0%) patients on combination therapy. The mean prednisone-equivalent oral corticosteroid dose was 8.4 mg/day for monotherapy and combination therapy patients at baseline and 7.7 and 7.6 mg/day, respectively, at month 6. Adverse events or laboratory abnormalities requiring TCZ dose modification were reported for 66 (13.0%) monotherapy and 130 (15.7%) combination therapy patients. Effectiveness at 6 months was similar between groups; mean (SD) change from baseline in Clinical Disease Activity Index (CDAI) was -20.3 (14.18) for monotherapy and -22.3 (16.09) for combination therapy (p=0.7347). CONCLUSIONS: In routine clinical practice, 38% of patients received TCZ as monotherapy. Persistence on monotherapy or in combination therapy with csDMARDs was high, with a slight trend towards a higher rate with combination therapy, and effectiveness was similar between groups.

Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring: results of an international, cross-sectional study (COMORA).

BACKGROUND: PATIENTS with rheumatoid arthritis (RA) are at increased risk of developing comorbid conditions. OBJECTIVES: To evaluate the prevalence of comorbidities and compare their management in RA patients from different countries worldwide. STUDY DESIGN: international, cross-sectional. PATIENTS: consecutive RA patients. DATA COLLECTED: demographics, disease characteristics (activity, severity, treatment), comorbidities (cardiovascular, infections, cancer, gastrointestinal, pulmonary, osteoporosis and psychiatric disorders). RESULTS: Of 4586 patients recruited in 17 participating countries, 3920 were analysed (age, 56±13 years; disease duration, 10±9 years (mean±SD); female gender, 82%; DAS28 (Disease Activity Score using 28 joints)-erythrocyte sedimentation rate, 3.7±1.6 (mean±SD); Health Assessment Questionnaire, 1.0±0.7 (mean±SD); past or current methotrexate use, 89%; past or current use of biological agents, 39%. The most frequently associated diseases (past or current) were: depression, 15%; asthma, 6.6%; cardiovascular events (myocardial infarction, stroke), 6%; solid malignancies (excluding basal cell carcinoma), 4.5%; chronic obstructive pulmonary disease, 3.5%. High intercountry variability was observed for both the prevalence of comorbidities and the proportion of subjects complying with recommendations for preventing and managing comorbidities. The systematic evaluation of comorbidities in this study detected abnormalities in vital signs, such as elevated blood pressure in 11.2%, and identified conditions that manifest as laboratory test abnormalities, such as hyperglycaemia in 3.3% and hyperlipidaemia in 8.3%. CONCLUSIONS: Among RA patients, there is a high prevalence of comorbidities and their risk factors. In this multinational sample, variability among countries was wide, not only in prevalence but also in compliance with recommendations for preventing and managing these comorbidities. Systematic measurement of vital signs and laboratory testing detects otherwise unrecognised comorbid conditions.

The importance of rheumatology biologic registries in Latin America.

Rheumatoid arthritis is a systemic inflammatory disorder characterized by joint articular pain and disability. Although there is scarcity of data available on the incidence and prevalence of RA in Latin America, there is a growing recognition of this disease where chronic diseases are on the rise and infectious disease on the decline. RA is a substantial burden to patients, society, and the healthcare system. The heterogeneity identified within RA presents an opportunity for personalized medicine, especially in regions with such demographic diversity as that of Latin America. To understand the long-term effects of treatment for RA especially on safety, registries have been established, a number of which have been created in Latin America. Despite their weaknesses (e.g., lack of controls and randomization), registries have provided additional and complementary information on the use of biologics in clinical practice in Latin America and other regions. Although certain challenges remain in the implementation and maintenance of registries, they continue to provide real-life data to clinical practice contributing to improved patient care.

Adherencia al tratamiento de pacientes con artritis reumatoidea que reciben medicamentos biológicos / Treatment adherence in patients with rheumatoid arthritis receiving biologics

Introducción: Al igual que en otras enfermedades crónicas, la adherencia al régimen terapéutico de los pacientes con artritis reumatoidea (AR) es baja (entre 30 y 80%), dependiendo de la definición de adherencia y de la metodología empleada para medirla. En este estudio se propone determinar el nivel de adherencia al tratamiento en pacientes con AR que reciben DMAR biológicas e identificar factores asociados a la falta de cumplimiento a la terapia. Material y métodos: Se realizó un estudio analítico, observacional de corte transversal en donde se incluyeron pacientes consecutivos con AR según criterios de clasificación (ACR’87) que se encontraban recibiendo fármacos biológicos para el tratamiento de su enfermedad en los últimos seis meses y que asistieron a la consulta ambulatoria. Para la valoración de la adherencia a DMAR se utilizaron los cuestionarios CQR (Compliance Questionnaire on Rheumatology) y el cuestionario SMAQ (Simplified Medication Adherence Questionnaire). Resultados: Se encuestaron 345 pacientes. Mediante el cuestionario SMAQ se observó una adherencia del 50% (159 pacientes). El Cuestionario CQR tuvo un puntaje mediano de 78 puntos (RIC 67-86). El 47% (147 pacientes) fueron adherentes (CQR >80). Sobre los pacientes incluidos, 151 (48%) refirieron no haber tenido ningún retraso, pérdida o adelanto de la dosis del biológico en los últimos 6 meses de tratamiento. El 52% no adherentes tuvo como causas: 146 (46%) pérdida de al menos una dosis del biológico con una mediana de dosis perdidas de 2 (RIQ: 1-3); 117 (37%) tuvo al menos un retraso en las dosis del biológico y 8 (2%) delantó la dosis. Los factores asociados al no cumplimiento de la terapia biológica fueron el tipo de cobertura médica, que el paciente no haya notado mejoría y la esperanza de una rápida respuesta al tratamiento, y la falta de adherencia a DMAR

Introduction: As in other chronic diseases, adherence to the therapeutic regimen of patients with rheumatoid arthritis (RA) is low (between 30 and 80%), depending on the definition of adherence and the methodology used to measure it. This study aims to determine the level of adherence to treatment in patients with RA who receive biological DMARs and to identify factors associated with non-compliance with therapy. MATERIAL AND METHODS: An observational, cross-sectional, observational study was performed in which consecutive patients with RA according to classification criteria (ACR'87) who were receiving biological drugs for the treatment of their disease in the last six months were included Attended the outpatient appointment. The CQR (Compliance Questionnaire on Rheumatology) and SMAQ (Simplified Medication Adherence Questionnaire) questionnaires were used to assess adherence to DMAR. Results: A total of 345 patients were surveyed. A 50% adherence (159 patients) was observed through the SMAQ questionnaire. The CQR Questionnaire had a median score of 78 points (RIC 67-86). 47% (147 patients) were adherent (CQR> 80). Regarding the patients included, 151 (48%) reported not having had any delay, loss or advancement of the biological dose in the last 6 months of treatment. The 52% of non-adherents had as causes: 146 (46%) loss of at least one dose of the biological with a median of doses lost of 2 (RIQ: 1-3); 117 (37%) had at least one biological dose delay and 8 (2%) delayed the dose. Factors associated with non-compliance with biological therapy were the type of medical coverage, the patient's perceived improvement and the expectation of a rapid response to treatment, and lack of adherence to DMAR.

The prevalence of rheumatoid arthritis in Argentina: a capture-recapture study in a city of Buenos Aires province.

OBJECTIVE: The objective of this study was to assess the prevalence of rheumatoid arthritis (RA) in the population of a city of 70,000 inhabitants located in Buenos Aires, Argentina. METHODS: Based on the hypothesis that RA is an underdiagnosed disease in Argentina, a capture-recapture method was applied. A local registry of RA patients of Luján City was taken as the primary source; a telephone survey was specifically carried out as a secondary source of information. Patients suspected of having RA were referred to a local hospital to be examined by a team of 12 rheumatologists. Anamnesis and physical examination were followed by hand and foot radiography and erythrocyte sedimentation rate and rheumatoid factor measurements. RESULTS: According to the American College of Rheumatology criteria, a prevalence rate of 0.94% (95% confidence interval [CI], 0.86%-1.02%) was found in the surveyed population; in agreement with other studies, this prevalence was higher in women when compared with men (for female, 1.54% [95% CI, 1.40%-1.69%]; for male, 0.40% [95% CI, 0.32%-0.49%]). CONCLUSION: The prevalence of RA in a representative sample of the population of a city from the central region of Argentina seems to be close to 1%.

Rayleigh-Taylor instabilities in reaction-diffusion systems inside Hele-Shaw cell modified by the action of temperature.

The influence of temperature in the buoyancy driven Rayleigh-Taylor instability of reaction-diffusion fronts is investigated experimentally in Hele-Shaw cells. The acid autocatalysis of chlorite-tetrathionate reaction coupled to molecular diffusion yields exothermic planar reaction-diffusion fronts separating two miscible reactant and product solutions. The resulting chemical front moves downwards invading the fresh reactants, leaving the products of the reaction behind it. The density of the product solution is higher than the reactant solution; hence, the traveling front is buoyantly unstable and develops density fingers in time (Rayleigh-Taylor instability) when the products are above the reactants. The kinetic constant of a chemical reaction varies due to thermal effects. This may stabilize the exothermic descending front when temperature is increased, so that the mixing zone decreases, modifying the fingering patterns, until it almost disappears. The authors study the influence of the temperature variation on the instability pattern figure observed in the chlorite-tetrathionate reaction for long times, corresponding to the nonlinear regime.