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.
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.
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.
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.
To describe comorbid conditions in patients with rheumatoid arthritis–associated interstitial lung disease (RA-ILD) and to analyze factors associated with multimorbidity.
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.
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).
In patients with RA, multimorbidity was associated with ILD, systemic inflammation, and advanced age.
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•Comorbid conditions are a major cause of morbidity and mortality in patients with rheumatoid arthritis (RA) and patients with interstitial lung disease (ILD).•ILD was independently associated with multimorbidity in patients with RA.•The most frequent comorbid conditions associated with RA-ILD were traditional cardiovascular risk factors, depression, and osteoporosis.•Other factors, such as ACPA titers and elevated CRP levels, were also associated with multimorbidity in cases with RA-ILD.
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.
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).
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).
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.
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.
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).
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).
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.
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.
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).
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.
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
, 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.
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.
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.
Design: Multicentre observational case-control study.
RID and COVID-19 from different centres in Andalusia.
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).
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).
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.
To analyze the efficacy and safety of rituximab (RTX) in connective tissue disease associated with interstitial lung disease (CTD-ILD).
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.
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;
= 0.530) or DLCO (55.9 vs. 52.2;
= 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);
= 0.015), time to initiation of RTX (1.01 (1.001-1.02);
= 0.029), and mycophenolate (0.202 (0.04-0.8);
= 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.
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.
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