Rate of severe and fatal infections in a cohort of patients with interstitial lung disease associated with rheumatoid arthritis: a multicenter prospective study.

Objective: To describe severe infection, foci of infection, microorganisms, associated factors, and impact on mortality in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Patients and methods: The study was based on a multicenter prospective cohort of patients with RA-ILD followed up from 2015 to 2023. The main outcome measures were incident severe infection and fatal infection. We evaluated infectious foci, etiologic agents, vaccination status, variables associated with lung function, and clinical-therapeutic variables in RA. The incidence rate (IR) for infection and mortality was calculated per 100 person-years, and 3 multivariate models were constructed to explore factors associated with infection. Results: We followed up 148 patients with RA-ILD for a median 56.7 months (699.3 person-years). During this period, 142 patients (96%) had at least 1 infection. A total of 368 infectious episodes were recorded, with an IR of 52.6 per 100 person-years. Of the 48 patients who died, 65% did so from infection. Respiratory infections were the most common first infection (74%), infection overall (74%), and fatal infection (80%) and were caused mostly by SARS CoV-2, Streptococcus pneumoniae, Pseudomonas aeruginosa, and influenza A virus. The factors associated with an increased risk of infection and death in patients with RA-ILD were age, inflammatory activity, and therapy with corticosteroids and immunosuppressants. Conclusion: Patients with RA-ILD have a high risk of serious infection, especially respiratory infection. Infection develops early, is recurrent, and is frequently fatal. The presence of associated factors such as advanced age, joint inflammation, and treatment highlight the importance of integrated and preventive medical care.

Exploring candidate biomarkers for rheumatoid arthritis through cardiovascular and cardiometabolic serum proteome profiling.

Introduction: RA patients are at higher risk of cardiovascular disease, influenced by therapies. Studying their cardiovascular and cardiometabolic proteome can unveil biomarkers and insights into related biological pathways. Methods: This study included two cohorts of RA patients: newly diagnosed individuals (n=25) and those with established RA (disease duration >25 years, n=25). Both cohorts were age and sex-matched with a control group (n=25). Additionally, a longitudinal investigation was conducted on a cohort of 25 RA patients treated with methotrexate and another cohort of 25 RA patients treated with tofacitinib for 6 months. Clinical and analytical variables were recorded, and serum profiling of 184 proteins was performed using the Olink technology platform. Results: RA patients exhibited elevated levels of 75 proteins that might be associated with cardiovascular disease. In addition, 24 proteins were increased in RA patients with established disease. Twenty proteins were commonly altered in both cohorts of RA patients. Among these, elevated levels of CTSL1, SORT1, SAA4, TNFRSF10A, ST6GAL1 and CCL18 discriminated RA patients and HDs with high specificity and sensitivity. Methotrexate treatment significantly reduced the levels of 13 proteins, while tofacitinib therapy modulated the expression of 10 proteins. These reductions were associated with a decrease in DAS28. Baseline levels of SAA4 and high levels of BNP were associated to the non-response to methotrexate. Changes in IL6 levels were specifically linked to the response to methotrexate. Regarding tofacitinib, differences in baseline levels of LOX1 and CNDP1 were noted between non-responder and responder RA patients. In addition, response to tofacitinib correlated with changes in SAA4 and TIMD4 levels. Conclusion: In summary, this study pinpoints molecular changes linked to cardiovascular disease in RA and proposes candidate protein biomarkers for distinguishing RA patients from healthy individuals. It also highlights how methotrexate and tofacitinib impact these proteins, with distinct alterations corresponding to each drug's response, identifying potential candidates, as SAA4, for the response to these therapies.

Analysis of comorbidity in rheumatoid arthritis-associated interstitial lung disease: a nested case-cohort study.

OBJECTIVES: To describe comorbid conditions in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and to analyze factors associated with multimorbidity. METHODS: Nested case-cohort study of 2 prospective cohorts: one with RA-ILD (cases) and another with RA but not ILD (controls). The cohorts were matched for age, sex, and time since diagnosis. Multimorbidity was defined as the co-occurrence of 2 or more chronic diseases, in addition to RA and ILD. We evaluated the comorbid conditions included in the Charlson Comorbidity Index, cardiovascular risk factors, neuropsychiatric conditions, and other frequent conditions in RA. We also recorded clinical-laboratory variables, inflammatory activity according to the 28-joint Disease Activity Score, C-reactive protein (CRP), physical function, and pulmonary function. We performed 2 multivariate analyses to identify factors associated with multimorbidity in RA and RA-ILD. RESULTS: The final study population comprised 110 cases and 104 controls. Multimorbidity was more frequent among cases than controls (80 [72.7] vs 60 [57.7]; p = 0.021). In both groups, multimorbidity was associated with ILD (OR [95% CI] 1.92 [1.03-3.59]; p = 0.039), age (OR [95% CI] 1.05 [1.01-1.08]; p = 0.004), CRP (OR [95% CI] 1.16 [1.05-1.29]; p = 0.003), and erosions (OR [95% CI] 1.05 [1.01-1.08]; p = 0.004); in the cases, it was associated with CRP (OR [95% CI] 1.17 [1.01-1.35]; p = 0.027), anti-citrullinated peptide antibody (OR [95% CI] 1.23 [1.14-13.02]; p = 0.049), and forced vital capacity (OR [95% CI] 0.79 [0.96-0.99]; p = 0.036). CONCLUSION: In patients with RA, multimorbidity was associated with ILD, systemic inflammation, and advanced age.

Hospitalizaciones y mortalidad por COVID-19 en pacientes con enfermedades inflamatorias reumáticas en Andalucía / Hospitalization and Mortality from COVID-19 of Patients with Rheumatic Inflammatory Diseases in Andalusia

Objetivo: Describir si las enfermedades inflamatorias reumáticas (EIR) se asocian con mayor riesgo de hospitalización y/o mortalidad por COVID-19 e identificar los factores asociados a la hospitalización y mortalidad en EIR y COVID-19 en diferentes hospitales de Andalucía.Métodos: Diseño: Estudio multicéntrico observacional de casos y controles.Pacientes Casos: EIR y COVID-19 de diferentes centros de Andalucía. Controles: pacientes sin EIR pareados por sexo, edad y PCR-COVID.Protocolo: Se solicitó al Servicio de Microbiología un listado de pacientes con PCR para COVID-19 desde 14 de marzo al 14 de abril de 2020. Se identificaron los pacientes que tuvieran EIR y luego consecutivamente un control pareado para cada caso. Variables La variable de desenlace principal fue ingreso hospitalario y mortalidad por COVID-19. Análisis estadístico Bivariante seguida de modelos de regresión logística binaria (variable dependiente: mortalidad/ingreso hospitalario).Resultados: Se incluyeron 156 pacientes con COVID-19, 78 con EIR y 78 sin EIR. Los pacientes con EIR no presentaron características de la enfermedad COVID-19 diferentes a la población general, tampoco mayor ingreso hospitalario ni mortalidad. El factor asociado con mortalidad en los pacientes con EIR fue edad (OR [IC 95%], 1,1 [1,0-1,2]; p = 0,025), mientras que los factores asociados con ingreso hospitalario fueron edad (OR [IC 95%], 1,1 [1,1-1,2]; p = 0,007) e hipertensión arterial (OR [IC 95%], 3,9 [1,5-6,7]; p = 0,003).Conclusión: La mortalidad y el ingreso hospitalario por COVID-19 no parecen aumentados en las EIR. La edad se asoció con mortalidad en EIR y, además, la hipertensión arterial se asoció con ingreso hospitalario.(AU)

Objective: To describe whether rheumatic inflammatory diseases (RID) are associated with a higher risk of hospitalization and/or mortality from COVID-19 and identify the factors associated with hospitalization and mortality in RID and COVID-19 in different Hospitals in Andalusia. Methods: Design: Multicentre observational case-control study. Patients: RID and COVID-19 from different centres in Andalusia. Controls: patients without RIS matched by sex, age and CRP-COVID. Protocol A list of patients with PCR for COVID-19 was requested from the microbiology service from March 14 to April 14, 2020. The patients who had RID were identified and then consecutively a paired control for each case. Variables The main outcome variable was hospital admission and mortality from COVID-19. Statistical analysis Bivariate followed by binary logistic regression models (DV: mortality/hospital admission).Results: One hundred and fifty-six patients were included, 78 with RID and COVID-19 and 78 without RID with COVID-19. The patients did not present characteristics of COVID-19 disease different from the general population, nor did they present higher hospital admission or mortality. The factor associated with mortality in patients with RID was advanced age (OR [95% CI], 1.1 [1.0-1.2]; p = 0.025), while the factors associated with hospitalization were advanced age (OR [95% CI], 1.1 [1.0-1.1]; p = 0.007) and hypertension (OR [95% CI], 3.9 [1.5-6.7]; p = 0.003).Conclusion: Mortality and hospital admission due to COVID-19 do not seem to increase in RID. Advanced age was associated with mortality in RID and, in addition, HTN was associated with hospital admission.(AU)

Safety and Effectiveness of Abatacept in a Prospective Cohort of Patients with Rheumatoid Arthritis-Associated Interstitial Lung Disease.

OBJECTIVE: To prospectively evaluate the safety and efficacy profile of abatacept in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: We performed a prospective observational multicenter study of a cohort of patients with RA-ILD treated with abatacept between 2015 and 2021. Patients were evaluated using high-resolution computed tomography and pulmonary function tests at initiation, 12 months, and the end of follow-up. The effectiveness of abatacept was evaluated based on whether ILD improved, stabilized, progressed, or was fatal. We also evaluated factors such as infection, hospitalization, and inflammatory activity using the 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR). Cox regression analysis was performed to identify factors associated with progression of lung disease. RESULTS: The study population comprised 57 patients with RA-ILD treated with abatacept for a median (IQR) of 27.3 (12.2-42.8) months. Lung disease had progressed before starting abatacept in 45.6% of patients. At the end of follow-up, lung disease had improved or stabilized in 41 patients (71.9%) and worsened in 13 (22.8%); 3 patients (5.3%) died. No significant decreases were observed in forced vital capacity (FVC) or in the diffusing capacity of the lung for carbon monoxide (DLCO).The factors associated with progression of RA-ILD were baseline DAS28-ESR (OR [95% CI], 2.52 [1.03-3.12]; p = 0.041), FVC (OR [95% CI], 0.82 [0.70-0.96]; p = 0.019), and DLCO (OR [95% CI], 0.83 [0.72-0.96]; p = 0.018). Only 10.5% of patients experienced severe adverse effects. CONCLUSION: Pulmonary function and joint inflammation stabilized in 71% of patients with RA-ILD treated with abatacept. Abatacept had a favorable safety profile.

Importance of Vaccination against SARS-CoV-2 in Patients with Interstitial Lung Disease Associated with Systemic Autoimmune Disease.

Objectives: To describe the frequency of COVID-19 and the effect of vaccination in patients with interstitial lung disease and systemic autoimmune disease (ILD-SAD) and to identify factors associated with infection and severity of COVID-19. Methods: We performed a cross-sectional multicenter study of patients with ILD-SAD followed between June and October 2021. The main variable was COVID-19 infection confirmed by a positive polymerase chain reaction (PCR) result for SARS-CoV-2. The secondary variables included severity of COVID-19, if the patient had to be admitted to hospital or died of the disease, and vaccination status. Other variables included clinical and treatment characteristics, pulmonary function and high-resolution computed tomography. Two logistic regression was performed to explore factors associated with "COVID-19" and "severe COVID-19". Results: We included 176 patients with ILD-SAD: 105 (59.7%) had rheumatoid arthritis, 49 (27.8%) systemic sclerosis, and 22 (12.54%) inflammatory myopathies. We recorded 22/179 (12.5%) SARS-CoV-2 infections, 7/22 (31.8%) of them were severe and 3/22 (13.22%) died. As to the vaccination, 163/176 (92.6%) patients received the complete doses. The factors associated with SARS-CoV-2 infection were FVC (OR (95% CI), 0.971 (0.946−0.989); p = 0.040), vaccination (OR (95% CI), 0.169 (0.030−0.570); p = 0.004), and rituximab (OR (95% CI), 3.490 (1.129−6.100); p = 0.029). The factors associated with severe COVID-19 were the protective effect of the vaccine (OR (95% CI), 0.024 (0.004−0.170); p < 0.001) and diabetes mellitus (OR (95% CI), 4.923 (1.508−19.097); p = 0.018). Conclusions: Around 13% of patients with ILD-SAD had SARS-CoV-2 infection, which was severe in approximately one-third. Most patients with severe infection were not fully vaccinated.

Subclinical Atherosclerosis Measure by Carotid Ultrasound and Inflammatory Activity in Patients with Rheumatoid Arthritis and Spondylarthritis.

OBJECTIVE: To compare the effect of inflammation on subclinical atherosclerosis using carotid ultrasound in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: Cross-sectional study including 347 participants (148 RA, 159 SpA, and 40 controls). We measured the carotid intima media thickness (cIMT) and detection of atheromatous plaques using carotid ultrasound. We recorded disease activity (DAS28-CRP/ASDAS-CRP) and traditional cardiovascular risk factors. We performed descriptive, bivariate, and linear multivariate analyses (dependent variable: cIMT) to evaluate the influence of diagnosis on cIMT in all patients. Two additional multivariate analyses were performed by stratifying patients according to their inflammatory activity. RESULTS: cIMT correlated with the mean CRP during the previous 5 years in RA, but not with CRP at the cut-off date. We did not find such differences in patients with SpA. The first multivariate model revealed that increased cIMT was more common in patients with RA than in those with SpA (ß coefficient, 0.045; 95% confidence interval (95% CI), 0.0002-0.09; p = 0.048) after adjusting for age, sex, disease course, and differential cardiovascular risk factors (arterial hypertension, smoking, statins, and corticosteroids). The second model revealed no differences in cIMT between the 2 groups of patients classified as remission-low activity (ß coefficient, 0.020; 95% CI, -0.03 to 0.080; p = 0.500). However, when only patients with moderate-high disease activity were analysed, the cIMT was 0.112 mm greater in those with RA (95% CI, 0.013-0.212; p = 0.026) than in those with SpA after adjusting for the same variables. CONCLUSIONS: Subclinical atherosclerosis measured by carotid ultrasound in patients with RA and SpA is comparable when the disease is well controlled. However, when patients have moderate-high disease activity, cIMT is greater in patients with RA than in those with SpA after adjusting for age, sex, disease course, and cardiovascular risk factors. Our results point to greater involvement of disease activity in subclinical atherosclerosis in patients with RA than in those with SpA.

Efficacy and Safety of Rituximab in Autoimmune Disease-Associated Interstitial Lung Disease: A Prospective Cohort Study.

OBJECTIVES: To analyze the efficacy and safety of rituximab (RTX) in connective tissue disease associated with interstitial lung disease (CTD-ILD). METHODS: We performed a multicenter, prospective, observational study of patients with CTD-ILD receiving rituximab between 2015 and 2020. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline, at 12 months, and at the end of follow-up. The main outcome measure at the end of follow-up was forced vital capacity (FVC) > 10% or diffusing capacity of the lungs for carbon monoxide (DLCO) > 15% and radiological progression or death. We recorded clinical characteristics, time to initiation of RTX, concomitant treatment, infections, and hospitalization. A Cox regression analysis was performed to identify factors associated with worsening ILD. RESULTS: We included 37 patients with CTD-ILD treated with RTX for a median (IQR) of 38.2 (17.7-69.0) months. At the end of the follow-up, disease had improved or stabilized in 23 patients (62.1%) and worsened in seven (18.9%); seven patients (18.9%) died. No significant decline was observed in median FVC (72.2 vs. 70.8; p = 0.530) or DLCO (55.9 vs. 52.2; p = 0.100). The multivariate analysis showed the independent predictors for worsening of CTD-ILD to be baseline DLCO (OR (95% CI), 0.904 (0.8-0.9); p = 0.015), time to initiation of RTX (1.01 (1.001-1.02); p = 0.029), and mycophenolate (0.202 (0.04-0.8); p = 0.034). Only 28 of the 37 patients (75.6%) were still undergoing treatment with RTX: two patients (5.4%) stopped treatment due to adverse events and seven patients (18.9%) died owing to progression of ILD and superinfection. CONCLUSION: Lung function improved or stabilized in more than half of patients with CTD-ILD treated with RTX. Early treatment and combination with mycophenolate could reduce the risk of progression of ILD.

Postprandial Hyperlipidemia: Association with Inflammation and Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis.

OBJECTIVE: To describe postprandial lipidemia in patients with rheumatoid arthritis (RA) and to analyze its association with subclinical atherosclerosis and inflammatory activity. METHODS: Observational study of 80 cases of RA and 80 sex- and age-matched controls. We excluded individuals with dyslipidemia. Postprandial hyperlipidemia (PPHL) was defined as postprandial triglycerides >220 mg/dL and/or postprandial ApoB48 levels >75th percentile (>p75). Plasma lipids, cholesterol, triglycerides, ApoB48, and total ApoB were evaluated at baseline and after a meal. Other variables analyzed included subclinical atherosclerosis (defined as presence of carotid atheromatous plaque), inflammatory activity (disease activity score (DAS28-ESR)), cytokines, apolipoproteins, and physical activity. A multivariate analysis was performed to identify factors associated with PPHL in patients with RA. RESULTS: A total of 75 patients with RA and 67 healthy controls fulfilled the inclusion criteria. PPHL was more frequent in patients with RA than controls (No. (%), 29 (38.70) vs. 15 (22.40); p = 0.036), as was subclinical atherosclerosis (No. (%), 22 (30.10) vs. 10 (14.90); p = 0.032). PPHL in patients with RA was associated with subclinical atherosclerosis (OR (95% CI) 4.69 (1.09-12.11); p = 0.037), TNF-α (OR (95% CI) 2.00 (1.00-3.98); p = 0.048), high-sensitivity C-reactive protein (OR (95% CI) 1.10 (1.01-1.19); p = 0.027), and baseline triglycerides (OR (95% CI) 1.02 (1.00-1.04); p = 0.049). CONCLUSION: PPHL was more frequent in patients with RA than in controls. PPHL in patients with RA was associated with inflammation and subclinical atherosclerosis.

Hospitalization and mortality from COVID-19 of patients with rheumatic inflammatory diseases in Andalusia.

OBJECTIVE: To describe whether rheumatic inflammatory diseases (RID) are associated with a higher risk of hospitalization and/or mortality from COVID-19 and identify the factors associated with hospitalization and mortality in RID and COVID-19 in different Hospitals in Andalusia. METHODS: Design: Multicentre observational case-COntrol study. PATIENTS: RID and COVID-19 from different centres in Andalusia. CONTROLS: patients without RIS matched by sex, age and CRP-COVID. Protocol A list of patients with PCR for COVID-19 was requested from the microbiology service from March 14 to April 14, 2020. The patients who had RID were identified and then consecutively a paired control for each case. Variables The main outcome variable was hospital admission and mortality from COVID-19. Statistical analysis Bivariate followed by binary logistic regression models (DV: mortality/hospital admission). RESULTS: One hundred and fifty-six patients were included, 78 with RID and COVID-19 and 78 without RID with COVID-19. The patients did not present characteristics of COVID-19 disease different from the general population, nor did they present higher hospital admission or mortality. The factor associated with mortality in patients with RID was advanced age (OR [95% CI], 1.1 [1.0-1.2]; P= .025), while the factors associated with hospitalization were advanced age (OR [95% CI], 1.1 [1.0-1.1]; P = .007) and hypertension (OR [95% CI], 3.9 [1.5-6.7]; P = .003). CONCLUSION: Mortality and hospital admission due to COVID-19 do not seem to increase in RID. Advanced age was associated with mortality in RID and, in addition, HTN was associated with hospital admission.

Efectividad, seguridad y análisis económico de Benepali en práctica clínica / Effectiveness, safety and economic analysis of Benepali in clinical practice

Objetivo: Evaluar la efectividad, la seguridad y los costes de etanercept biosimilar (BS) en pacientes con artritis reumatoide (AR), espondiloartritis (EspA) y artritis psoriásica (APs) y en comparación con su original, en condiciones de práctica clínica habitual. Pacientes y métodos: Estudio observacional retrospectivo. Se incluyeron 138 pacientes con AR, EspA o APs tratados con al menos una dosis de Benepali® (n=79) o Enbrel® (n=59). Como desenlace principal de efectividad del BS o de su original se usó el tiempo de retención del fármaco. Como desenlace secundario de efectividad se midió la proporción de pacientes que alcanzaban baja actividad o remisión a las 52semanas. La seguridad fue evaluada mediante tasas de incidencia de efectos adversos. Se hizo un análisis de minimización de costes. Resultados: No se observaron diferencias en cuanto a retención del tratamiento (mediana [intervalo de confianza del 95%, IC95%] de 12,0meses [10,2-12,0] para BS y 12,0 meses [12,0-12,0] para el original). Se obtuvieron mejorías similares después de 52semanas en actividad inflamatoria y función física, excepto en los pacientes con EspA y APs, que en general obtuvieron mejores valores de BASDAI y ASDAS con el BS. No se registraron diferencias en el número total de efectos adversos (0,43 eventos/pacientes-año con BS frente a 0,53 con original). El uso del BS, en lugar de su original, supuso un ahorro neto para el centro de 118.383,55€ (1.747,2€/pacientes-año). Conclusiones: El uso del BS parece tan eficaz y seguro como su original y mucho más coste-efectivo.(AU)

Objective: To assess the effectiveness, safety and cost of Etanercept biosimilar in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA) compared to the standard drug in real clinical practice. Patients and methods: Retrospective observational study. Case series of 138 patients with RA, SpA or PsA treated with at least one dose of Benepali® (n=79) or Enbrel® (n=59). Drug retention time was the primary efficacy endpoint compared to the biosimilar and the original. The proportion of patients achieving low disease activity or remission after 52weeks was used as the secondary outcome. Safety was assessed by means of the adverse effects incidence rate. A cost minimization analysis was performed. Results: No differences were observed regarding treatment retention time between drugs (median [95% confidence interval, 95%CI] at 12.0months [10.2-12.0] for the biosimilar and 12.0months [12.0-12.0] for the original). Similar improvements, in terms of inflammatory activity and physical function, were obtained after 52weeks except for patients with SpA and PsA who, in general, experienced improvements of BASDAI and ASDAS with the original compared with the biosimilar. No significant differences were observed in the total number of adverse effects (.43 events/patient-years versus the biosimilar and .53 versus the original). Using the biosimilar in place of the original drug resulted in a net savings of 118,383.55€ (1,747.20€/patient-years) for the hospital. Conclusion: The biosimilar Benepali is as effective and safe as the original and much more cost-effective.(AU)

Effectiveness, safety and economic analysis of Benepali in clinical practice.

OBJECTIVE: To assess the effectiveness, safety and cost of Etanercept biosimilar in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA) compared to the standard drug in real clinical practice. PATIENTS AND METHODS: Retrospective observational study. Case series of 138 patients with RA, SpA or PsA treated with at least one dose of Benepali® (n = 79) or Enbrel® (n = 59). Drug retention time was the primary efficacy endpoint compared to the biosimilar and the original. The proportion of patients achieving low disease activity or remission after 52 weeks was used as the secondary outcome. Safety was assessed by means of the adverse effects incidence rate. A cost minimization analysis was performed. RESULTS: No differences were observed regarding treatment retention time between drugs (median [95% confidence interval, 95% CI] at 12.0 months [10.2-12.0] for the biosimilar and 12.0 months [12.0-12.0] for the original). Similar improvements, in terms of inflammatory activity and physical function, were obtained after 52 weeks except for patients with SpA and PsA who, in general, experienced improvements of BASDAI and ASDAS with the original compared with the biosimilar. No significant differences were observed in the total number of adverse effects (.43 events/patient-years versus the biosimilar and .53 versus the original). Using the biosimilar in place of the original drug resulted in a net savings of 118,383.55 € (1,747.20 €/patient-years) for the hospital. CONCLUSION: The biosimilar Benepali is as effective and safe as the original and much more cost-effective.

Characteristics and Predictors of Progression Interstitial Lung Disease in Rheumatoid Arthritis Compared with Other Autoimmune Disease: A Retrospective Cohort Study.

OBJECTIVES: To describe the characteristics and progression of interstitial lung disease in patients with associated systemic autoimmune disease (ILD-SAI) and to identify factors associated with progression and mortality. PATIENTS AND METHODS: We performed a multicenter, retrospective, observational study of patients with ILD-SAI followed between 2015 and 2020. We collected clinical data and performed pulmonary function testing and high-resolution computed tomography at diagnosis and at the final visit. The main outcome measure at the end of follow-up was forced vital capacity (FVC) >10% or diffusing capacity of the lungs for carbon monoxide >15% and radiological progression or death. Cox regression analysis was performed to identify factors associated with worsening of ILD. RESULTS: We included 204 patients with ILD-SAI: 123 (60.3%) had rheumatoid arthritis (RA), 58 had (28.4%) systemic sclerosis, and 23 (11.3%) had inflammatory myopathy. After a median (IQR) period of 56 (29.8-93.3) months, lung disease had stabilized in 98 patients (48%), improved in 33 (16.1%), and worsened in 44 (21.5%). A total of 29 patients (14.2%) died. Progression and hospitalization were more frequent in patients with RA (p = 0.010). The multivariate analysis showed the independent predictors for worsening of ILD-SAI to be RA (HR, 1.9 [95% CI, 1.3-2.7]), usual interstitial pneumonia pattern (HR, 1.7 [95% CI, 1.0-2.9]), FVC (%) (HR, 2.3 [95% CI, 1.4-3.9]), and smoking (HR, 2.7 [95%CI, 1.6-4.7]). CONCLUSION: Disease stabilizes or improves after a median of 5 years in more than half of patients with ILD-SAI, although more than one-third die. Data on subgroups and risk factors could help us to predict poorer outcomes.

Hospitalization and Mortality from COVID-19 of Patients with Rheumatic Inflammatory Diseases in Andalusia. / Hospitalizaciones y mortalidad por COVID-19 en pacientes con enfermedades inflamatorias reumáticas en Andalucía.

OBJECTIVE: To describe whether rheumatic inflammatory diseases (RID) are associated with a higher risk of hospitalization and/or mortality from COVID-19 and identify the factors associated with hospitalization and mortality in RID and COVID-19 in different Hospitals in Andalusia. METHODS: Design: Multicentre observational case-control study. PATIENTS: RID and COVID-19 from different centres in Andalusia. CONTROLS: patients without RIS matched by sex, age and CRP-COVID. Protocol A list of patients with PCR for COVID-19 was requested from the microbiology service from March 14 to April 14, 2020. The patients who had RID were identified and then consecutively a paired control for each case. Variables The main outcome variable was hospital admission and mortality from COVID-19. Statistical analysis Bivariate followed by binary logistic regression models (DV: mortality/hospital admission). RESULTS: One hundred and fifty-six patients were included, 78 with RID and COVID-19 and 78 without RID with COVID-19. The patients did not present characteristics of COVID-19 disease different from the general population, nor did they present higher hospital admission or mortality. The factor associated with mortality in patients with RID was advanced age (OR [95% CI], 1.1 [1.0-1.2]; p = 0.025), while the factors associated with hospitalization were advanced age (OR [95% CI], 1.1 [1.0-1.1]; p = 0.007) and hypertension (OR [95% CI], 3.9 [1.5-6.7]; p = 0.003). CONCLUSION: Mortality and hospital admission due to COVID-19 do not seem to increase in RID. Advanced age was associated with mortality in RID and, in addition, HTN was associated with hospital admission.

Predictors of Progression and Mortality in Patients with Prevalent Rheumatoid Arthritis and Interstitial Lung Disease: A Prospective Cohort Study.

OBJECTIVES: To describe a prospective cohort of patients with rheumatoid arthritis associated with interstitial lung disease (RA-ILD) and identify risk factors associated with disease progression and mortality in this cohort. PATIENTS AND METHODS: We performed a multicenter, prospective, observational study of patients with RA-ILD receiving disease-modifying antirheumatic drugs (DMARDs) between 2015 and 2020. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline and at 60 months. The main endpoint was "Progression to ILD at the end of follow-up" in terms of the following outcomes: (1) improvement (i.e., improvement in forced vital capacity (FVC) ≥10% or diffusing capacity of the lungs for carbon monoxide (DLCO) ≥15% and absence of radiological progression); (2) nonprogression (stabilization or improvement in FVC ≤10% or diffusing capacity of the lungs for carbon monoxide (DLCO) <15% and absence of radiological progression); (3) progression (worsening of FVC >10% or DLCO >15% and radiological progression); or (4) death. We recorded demographic and clinical characteristics, lung function, and the incidence of adverse events. A Cox regression analysis was performed to identify factors associated with the worsening of ILD. RESULTS: After 60 months, lung disease had stabilized in 66 patients (56.9%), improved in 9 (7.8%), and worsened in 23 (19.8%). Eighteen patients (15.5%) died, with a mean survival of 71.8 (1.9) months after diagnosis of ILD. The Cox multivariate analysis revealed the independent predictors of worsening of RA-ILD to be usual interstitial pneumonia (hazard ratio (HR), 2.6 (95%CI, 1.0-6.7)), FVC <80% (HR, 3.8 (95%CI, 1.5-6.7)), anticitrullinated protein antibody titers (HR, 2.8 (95%CI, 1.1-6.8)), smoking (HR, 2.5 (95%CI, 1.1-6.2)), and treatment with abatacept, tocilizumab, or rituximab (HR, 0.4 (95%CI, 0.2-0.8)). During follow-up, 79 patients (68%) experienced an adverse event, mostly infection (61%). Infection was fatal in 10/18 patients (55.5%) during follow-up. CONCLUSIONS: Lung function is stable in most patients with RA-ILD receiving treatment with disease-modifying anti-rheumatic drugs (DMARDs), although one-third worsened or died. Identifying factors associated with worsening in RA-ILD is important for clinical management.

Association between Carotid Intima-Media Thickness and the Use of Biological or Small Molecule Therapies in Patients with Rheumatoid Arthritis.

OBJECTIVE: The objective of this study was to assess the association of carotid intima-media thickness (CIMT), and also the presence of atheromatous plaque, with biological and targeted synthetic disease-modifying antirheumatic drugs, in an established cohort of patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: We conducted a cross-sectional observational study based on a cohort of patients with RA and a registry of healthy controls, in whom the CIMT and presence of atheromatous plaque were assessed by ultrasound. Data were collected on disease activity, lab results and treatments. Descriptive and bivariate analyses were performed and two multivariate linear regression models (with CIMT as the dependent variable) were constructed to identify variables independently associated with CIMT in our sample of patients with RA. RESULTS: A total of 176 individuals (146 patients with RA and 30 controls) were included. A higher percentage of patients than controls had atheromatous plaque (33.8% vs. 12.5%, p = 0.036), but no differences were found in terms of CIMT (0.64 vs. 0.61, p = 0.444). Compared to values in patients on other therapies, the CIMT was smaller among patients on tumour necrosis factor alpha (TNFα) inhibitors (mean [SD]: 0.58 [0.10] vs. 0.65 [0.19]; p = 0.013) and among those on Janus kinase inhibitors (mean [SD]: 0.52 [0.02] vs. 0.64 [0.18]; p < 0.001), while no differences were found as a function of the use of the other therapies considered. The multivariate linear regression analysis to identify factors associated with CIMT in our patients, adjusting for traditional cardiovascular risk factors such as hypertension, high levels of low-density lipoproteins, diabetes mellitus and smoking, showed that male sex, older age and having a greater cumulative erythrocyte sedimentation rate were independently associated with a larger CIMT, while patients on TNFα inhibitors had a CIMT 0.075 mm smaller than those on other treatments. CONCLUSIONS: The use of TNFα inhibitors may protect against subclinical atherosclerosis in patients with RA, patients on this biologic having smaller CIMTs than patients on other disease-modifying antirheumatic drugs. Nonetheless, these results should be confirmed in prospective studies with larger sample sizes.

Postprandial Apolipoprotein B48 is Associated with Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis.

OBJECTIVE: To describe postprandial lipemia in patients with rheumatoid arthritis (RA) and to analyze its association with subclinical atherosclerosis measured as carotid intima-media thickness (cIMT). METHODS: We performed an observational study of 40 patients with RA and 40 sex and age-matched controls. Patients with dyslipidemia were excluded. Pathologically increased cIMT was defined as a carotid thickness greater than the 90th percentile (>p90) for age and sex. Fasting and postprandial plasma lipids, cholesterol, triglycerides, apolipoprotein B48 (ApoB48), and total ApoB were evaluated. The other variables included were clinical and laboratory values, Framingham score, and the 28-joint Disease Activity Score (DAS28). Two multivariate models were constructed to identify factors associated with pathologic cIMT in patients with RA. RESULTS: Fasting lipid values were similar in patients with RA and controls, although those of postprandial ApoB48 were higher (median (IQR), 14.4 (10.8-12.1) vs. 12.1 (2.3-9,8); p = 0.042). Pathologic cIMT was recorded in 10 patients with RA (25%) and nine controls (22.5%). In patients with RA, pathologic cIMT was associated with postprandial ApoB48 (OR (95% CI), 1.15 (1.0-1.3)) and total ApoB (OR [95% CI], 1.12 [1.1-1.2]). The second model revealed a mean increase of 0.256 mm for cIMT in patients with elevated anticitrullinated protein antibodies (ACPAs). CONCLUSION: Postprandial ApoB48 levels in patients with RA are higher than in controls. Postprandial ApoB48 and total ApoB levels and markers of severity, such as ACPAs, are associated with pathologic cIMT in patients with RA. Our findings could indicate that these atherogenic particles have a negative effect on the endothelium.

Análisis de la efectividad, seguridad y optimización de tocilizumab en una cohorte de pacientes con artritis reumatoide en práctica clínica / Analysis of effectiveness, safety and optimization of tocilizumab in a cohort of patients with rheumatoid arthritis in clinical practice

Objetivo: Evaluar la efectividad y la seguridad de tocilizumab (TCZ) en pacientes con artritis reumatoide (AR) en práctica clínica; la optimización de dosis y el cambio de formulación intravenosa (iv) a subcutánea (sc). Material y métodos: Estudio observacional retrospectivo. Se incluyó a 53 pacientes con AR tratados con TCZ. El desenlace principal fue efectividad de TCZ en la semana 24. Variables de desenlace secundarias incluyeron: efectividad en la semana 52, tiempo de retención del tratamiento, función física y seguridad. También se midió efectividad de la optimización de dosis y del cambio de formulación iv a sc a los 3 y 6 meses. La efectividad se midió con el índice de actividad según el Disease activity score-28. Se usó la prueba T pareada o prueba de rangos con signos de Wilcoxon para evaluar efectividad y el tiempo de supervivencia mediante curvas de Kaplan-Meier. Resultados: La proporción de pacientes que alcanzaron la remisión o baja actividad de la enfermedad en las semanas 24 y 52 fue del 75,5 y el 87,3%, respectivamente. La media de tiempo de retención (intervalo de confianza del 95% [IC del 95%]) fue de 81,7 meses (76,6-86,7). Veintiuno de 53 pacientes (39,6%) optimizaron la dosis de TCZ y 35 pacientes cambiaron a TCZ sc desde iv, sin cambios en resultados de efectividad. La tasa de efectos adversos fue 13,6 eventos/100 pacientes-año. Conclusiones: Tocilizumab parece efectivo y seguro en AR en práctica clínica. La reducción de dosis parece efectiva en la mayoría de los pacientes en remisión, incluso cuando cambian de iv a sc

Objective: To evaluate the effectiveness and safety of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, establishing the optimized regimen and switching from intravenous (IV) to subcutaneous (SC) therapy. Material and methods: Retrospective observational study. We included 53 RA patients treated with TCZ. The main outcome was TCZ effectiveness at week 24. Secondary outcome variables included effectiveness at week 52, therapeutic maintenance, physical function and safety. The effectiveness of optimization and the switch from IV to SC was evaluated at 3 and 6 months. The efficacy was measured with the Disease Activity Score. Paired t-tests or Wilcoxon were used to evaluate effectiveness and survival time using Kaplan-Meier. Results: The proportion of patients who achieved remission or low disease activity at weeks 24 and 52 was 75.5% and 87.3%, respectively. The mean retention time (95% confidence interval [95% CI] was 81.7 months [76.6-86.7]). Twenty-one of 53 patients (39.6%) optimized the TCZ dose and 35 patients switched from IV TCZ to SC, with no changes in effectiveness. The adverse event rate was 13.6 events/100 patient-years. Conclusions: Tocilizumab appears to be effective and safe in RA in clinical practice. The optimized regimen appears to be effective in most patients in remission, even when they change from IV to SC

Analysis of effectiveness, safety and optimization of tocilizumab in a cohort of patients with rheumatoid arthritis in clinical practice. / Análisis de la efectividad, seguridad y optimización de tocilizumab en una cohorte de pacientes con artritis reumatoide en práctica clínica.

OBJECTIVE: To evaluate the effectiveness and safety of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, establishing the optimized regimen and switching from intravenous (IV) to subcutaneous (SC) therapy. MATERIAL AND METHODS: Retrospective observational study. We included 53 RA patients treated with TCZ. The main outcome was TCZ effectiveness at week 24. Secondary outcome variables included effectiveness at week 52, therapeutic maintenance, physical function and safety. The effectiveness of optimization and the switch from IV to SC was evaluated at 3 and 6 months. The efficacy was measured with the Disease Activity Score. Paired t-tests or Wilcoxon were used to evaluate effectiveness and survival time using Kaplan-Meier. RESULTS: The proportion of patients who achieved remission or low disease activity at weeks 24 and 52 was 75.5% and 87.3%, respectively. The mean retention time (95% confidence interval [95% CI] was 81.7 months [76.6-86.7]). Twenty-one of 53 patients (39.6%) optimized the TCZ dose and 35 patients switched from IV TCZ to SC, with no changes in effectiveness. The adverse event rate was 13.6 events/100 patient-years. CONCLUSIONS: Tocilizumab appears to be effective and safe in RA in clinical practice. The optimized regimen appears to be effective in most patients in remission, even when they change from IV to SC.

Adherence of rheumatoid arthritis patients to biologic disease-modifying antirheumatic drugs: a cross-sectional study.

The aims of this study were to evaluate adherence of rheumatoid arthritis (RA) patients to biological disease-modifying antirheumatic drugs (bDMARDs), identify potential risk factors, and analyze the discriminative ability of the Morisky-Green test (MGT) to detect bDMARD nonadherence. One hundred and seventy-eight adult RA patients treated with bDMARDs were included. Adherence was measured using the medication possession ratio (MPR) of the previous 6 months. An MPR >80% was considered good adherence. Patient demographics, clinical characteristics, and MGT scores were assessed through a standardized clinical interview at the cross-sectional date. One-hundred and twelve patients (63%) were taking subcutaneous bDMARDs, while 66 (37%) were taking intravenous drugs. One-hundred fifty-eight (88.8%) showed good adherence to bDMARDs, while 79 (61.2%) also correctly took concomitant conventional synthetic DMARDs (csDMARDs). In logistic regression models, nonadherence to bDMARDs was associated with higher disease activity [odds ratio (OR) 1.45; 95% CI, 1.03-2.03; p = 0.032] and subcutaneous route (OR 3.70; 95% CI 1.02-13.48; p = 0.040). MGT accurately identified an MPR >80% of bDMARDs in 76.9% of the patients. A sensitivity of 78%, specificity of 70%, positive predictive value of 95.3%, negative predictive value of 28.5%, positive likelihood ratio (LR) of 2.6, and negative LR of 0.3% were obtained. Adherence may be good for bDMARDs but is low for csDMARDs. Low adherence for bDMARDs is associated with poorer disease control during the past 6 months and use of subcutaneous route. These findings should alert doctors to consider possible low adherence before declaring treatment failure.