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.

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.

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.

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.

Ability to Participate in Social Activities of Rheumatoid Arthritis Patients Compared with Other Rheumatic Diseases: A Cross-Sectional Observational Study.

OBJECTIVES: To compare the ability to participate in social activities among rheumatoid arthritis patients with other rheumatic disease patients and identify potentially implicated factors. PATIENTS AND METHODS: Between June and November 2019, we consecutively selected patients aged ≥18 years with RA (defined according to ACR/EULAR 2010), SpA (ASAS/EULAR 2010), and SLE (ACR 1997). MAIN OUTCOME MEASURES: Ability to participate in social roles and activities evaluated using the PROMIS score v2.0 short-form 8a (PROMIS-APS). SECONDARY OUTCOMES: Participation in social activities according to a series of variables (mobility, depression, satisfaction with social relationships, social isolation, company, emotional support, instrumental support, and support via information). We evaluated the association between the ability to participate in social activities and associated variables using multivariable linear regression analysis. RESULTS: The study population comprised 50 patients with RA (33.1%), 51 patients (33.8%) with SpA, and 50 patients (33.1%) with SLE. The mean PROMIS-APS scores were similar in the three groups. The multivariable analysis for the whole sample showed that the ability to participate in social activities was inversely associated with depression and directly with social satisfaction, mobility, company, and age. The stratified analysis revealed an inverse association between inflammatory activity and ability to participate in social activities in patients with RA and SpA, but not in those with SLE. CONCLUSION: All patients with RA, SpA, and SLE had a similar ability to participate in social activities. This was associated with other psychosocial factors (social satisfaction, mobility, company, depression) and clinical factors (age and inflammatory activity).

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.

Integrative Clinical, Molecular, and Computational Analysis Identify Novel Biomarkers and Differential Profiles of Anti-TNF Response in Rheumatoid Arthritis.

Background: This prospective multicenter study developed an integrative clinical and molecular longitudinal study in Rheumatoid Arthritis (RA) patients to explore changes in serologic parameters following anti-TNF therapy (TNF inhibitors, TNFi) and built on machine-learning algorithms aimed at the prediction of TNFi response, based on clinical and molecular profiles of RA patients. Methods: A total of 104 RA patients from two independent cohorts undergoing TNFi and 29 healthy donors (HD) were enrolled for the discovery and validation of prediction biomarkers. Serum samples were obtained at baseline and 6 months after treatment, and therapeutic efficacy was evaluated. Serum inflammatory profile, oxidative stress markers and NETosis-derived bioproducts were quantified and miRNomes were recognized by next-generation sequencing. Then, clinical and molecular changes induced by TNFi were delineated. Clinical and molecular signatures predictors of clinical response were assessed with supervised machine learning methods, using regularized logistic regressions. Results: Altered inflammatory, oxidative and NETosis-derived biomolecules were found in RA patients vs. HD, closely interconnected and associated with specific miRNA profiles. This altered molecular profile allowed the unsupervised division of three clusters of RA patients, showing distinctive clinical phenotypes, further linked to the TNFi effectiveness. Moreover, TNFi treatment reversed the molecular alterations in parallel to the clinical outcome. Machine-learning algorithms in the discovery cohort identified both, clinical and molecular signatures as potential predictors of response to TNFi treatment with high accuracy, which was further increased when both features were integrated in a mixed model (AUC: 0.91). These results were confirmed in the validation cohort. Conclusions: Our overall data suggest that: 1. RA patients undergoing anti-TNF-therapy conform distinctive clusters based on altered molecular profiles, which are directly linked to their clinical status at baseline. 2. Clinical effectiveness of anti-TNF therapy was divergent among these molecular clusters and associated with a specific modulation of the inflammatory response, the reestablishment of the altered oxidative status, the reduction of NETosis, and the reversion of related altered miRNAs. 3. The integrative analysis of the clinical and molecular profiles using machine learning allows the identification of novel signatures as potential predictors of therapeutic response to TNFi therapy.

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.

Utility of pulmonary ultrasound to identify interstitial lung disease in patients with rheumatoid arthritis.

OBJECTIVES: To analyze the diagnostic utility of lung ultrasound (US) to detect interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients comparing with high-resolution computed tomography (HRCT) PATIENTS AND METHODS: We performed a cross-sectional, observational study in patients with RA-ILD (cases) controlled with a group of RA patients without ILD (controls) paired by sex, age, and time of disease evolution. Patients were assessed using HRCT, PFT, and US. The main variables were B-line number, evaluation of the lung-US score already described, pleural irregularities, and A pattern US lost. ROC curve analysis was performed to establish the cut-off point of the US B-lines number for detecting the presence of significant RA-ILD in relation to HRCT, and logistic regression analysis was performed to identify the intercostal spaces. RESULTS: Seventy-one patients were included, 35 (49.2%) with ILD-RA and 36 (50.8%) RA controls. Regarding US score, we found that the detection of 5.5 lines in a reduced score of 8 intercostal spaces had a sensitivity = 62.2%, specificity = 91.3%, PPV = 88.4%, and NPV = 69.5%. In multivariate analysis, the intercostal spaces which showed independent association with ILD were 3rd right anterior axillary space (OR [IC 95%] 19.0 [1.3-27.5]), 8th right posterior axillary space (OR [IC 95%] 0.04 [0.0-0.6]), 8th right subscapular space (OR [IC 95%] 16.5 [1.8-45.5]), 9th right paravertebral space (OR [IC 95%] 7.11 [1.0-37.1]), and 2nd left clavicular middle space (OR [IC 95%] 21.9 [1.26-37.8]). CONCLUSIONS: Lung ultrasound could be a useful tool for ILD diagnosis associated with rheumatoid arthritis. A 8-space reduced score showed a similar total predictive capacity than 72-space score. Key Points • Lung ultrasound could be a useful tool for ILD diagnosis associated with rheumatoid arthritis. • The 72-space evaluation is highly sensitive, whereas a simplified score enables a more specific and faster diagnosis. • The number of B lines is correlated with DLCO, ACPA, inflammatory activity, and physical function.

Non-anti-TNF biologic agents are associated with slower worsening of interstitial lung disease secondary to rheumatoid arthritis.

OBJECTIVES: To analyze the effect of disease-modifying antirheumatic drugs (DMARDs) on the outcome of interstitial lung disease secondary to rheumatoid arthritis (RA-ILD). PATIENTS AND METHODS: We performed a multicenter, prospective, observational study of patients with RA-ILD receiving DMARDs between 2015 and 2017. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline and at 24 months. The radiological assessment was centralized. The main outcome measure at 24 months was changed in lung function (improvement, stabilization, worsening, or death). We recorded the 28-joint Disease Activity Score 28 (DAS28) and adverse events. A logistic regression analysis was performed to identify factors associated with worsening of ILD. RESULTS: After 24 months, lung disease was stabilized in 40 patients (57.1%), improved in 8 (11.4%), and worse in 21 (30.0%). One patient (1.4%) died. The factors associated with worsening of ILD in the multivariate analysis were treatment with abatacept, tocilizumab, or rituximab (OR, 0.102 [95%CI, 0.015-0.686]), DAS28 (OR, 1.969 [95%CI, 1.005-3.857]), and smoking (OR, 6.937 [95%CI, 1.378-4.900]). During follow-up, 30 patients (42.9%) experienced an adverse event, which was severe in 12 cases (17.1%). CONCLUSIONS: Lung function is stable and inflammatory activity well controlled in most patients with RA-ILD receiving treatment with DMARDs. Non-anti-TNF DMARDs reduce the risk of worsening of lung disease in 90% of patients. The inflammatory activity of RA and smoking, on the other hand, are associated with worsening. Key Points • We have performed prospectively evaluated lung and joint function in patients with RA-ILD receiving treatment with various DMARDs. • In our study, the lung function is stable and inflammatory activity well controlled in most patients with RA-ILD receiving treatment with DMARDs. • Neither csDMARDs nor anti-TNF agents were associated with a significant risk of worsening of lung disease, whereas non-anti-TNF bDMARDs could reduce the risk of worsening of lung disease. • Smoking and poor control of joint involvement were the main factors associated with worsening of lung disease.

Analysis of Clinical-Analytical Characteristics in Patients with Rheumatoid Arthritis and Interstitial Lung Disease: Case-Control Study. / Análisis de las características clínico-analíticas de pacientes con artritis reumatoide y enfermedad pulmonar intersticial: casos y controles.

OBJECTIVES: To study the differences between rheumatoid arthritis (RA)-interstitial lung disease (ILD) patients and RA patients without ILD in severity markers and disease activity and to identify factors associated with the presence of ILD in RA patients. PATIENTS AND METHODS: Patients: RA-ILD patients selected from a multicentre cohort in Andalusia, Spain. CONTROLS: RA-patients without ILD paired by sex, age and disease duration. PROTOCOL: RA patients are reviewed every 3-6months in rheumatology consultation. All patients are reviewed according to a predetermined protocol with systematic data collection. OUTCOMES: description of ILD type, differences in severity markers and disease activity in both groups. Other variables: ILD type by imaging technique (HRCT): nonspecific interstitial pneumonia (NSIP)/usual interstitial pneumonia (UIP). Lung function by PTF. Activity and severity markers of arthritis by DAS28-ESR, HAQ, RF, ACPA and erosions. Treatment with DMARD. STATISTICAL ANALYSIS: descriptive and paired T-test or Chi-square test followed by binary logistic regression (DV: ILD in patients with RA). RESULTS: Eighty-two patients were included, 41 RA-ILD and 41 RA controls. RF and ACPA positivity, serositis and osteoporosis were more frequent in RA-ILD patients. No significant differences in DAS28 were observed (P=.145) between RA-ILD and RA control patients. RA-ILD patients presented worse HAQ scores (P=.006). All patients were treated with disease modifying antirheumatic drugs (DMARDs). The risk of developing ILD in RA patients is tripled by a history of smoking or the presence of erosive arthritis (R2=.36). CONCLUSIONS: The results of our study support the higher frequency of UIP and NSIP in RA patients. DLCO is the most sensitive parameter to detect ILD in RA patients. Our study showed that ILD in RA patients was associated with RA severity (presence of erosions and ACPA) and with a history of smoking.

Eficiencia de diferentes dosis de rituximab en la artritis reumatoide / Eficiency of different doses of rituximab in rheumatoid arthritis

OBJETIVO: Evaluar la efectividad, seguridad y coste de rituximab en pacientes con artritis reumatoide (AR) dependiendo de la dosis utilizada. MATERIAL Y MÉTODOS: Estudio observacional retrospectivo. Se incluyó a 52 pacientes con AR tratados al menos con una dosis de rituximab durante 135,3 pacientes-año. Se obtuvieron 3 grupos de tratamiento: G1, primer curso y siguientes de 2 infusiones de 1g separadas 15 días; G2, primer curso de 2 infusiones de 1g seguido por cursos de 2 infusiones de 500mg, y G3, primer curso y siguientes de 2 infusiones de 500mg separadas por 15 días. Los retratamientos fueron a demanda según la clínica. Se analizaron por grupos: el tiempo retención (Log-Rank), las tasas de retratamientos y de eventos adversos (razón de tasas de incidencia) y los costes del tratamiento por paciente-mes de rituximab. RESULTADOS: El grupo 2 mostró una mejor relación coste-efectividad que el grupo 1 ya que se asoció a una mayor retención de rituximab (media [IC del 95%] 65,7 [60,8-70,7] meses vs. 33,5 [22,7-44,3]; p < 0,001) y una menor tasa de eventos adversos graves, con solo un ligero incremento de la tasa de retratamientos (cursos/paciente-año [IC del 95%] 1,66 [1,39-1,93] vs. 1,01 [0,69.-1,34]; p = 0,005) y del coste (mediana/paciente-mes, 484,89 € vs. 473,45 €). Aunque el grupo 3 fue 41,20 €/paciente-mes más económico que el grupo 2, se asoció a una mayor tasa de retratamientos y una menor retención de rituximab (p < 0,001). CONCLUSIONES: El uso de rituximab a dosis completa al inicio seguido de dosis reducida en los sucesivos cursos administrados a demanda parece la opción más coste-efectiva

OBJECTIVE: Evaluate the effectiveness, cost and safety of rituximab in patients with rheumatoid arthritis (RA) depending on the dose used. MATERIAL AND METHODS: Retrospective observational study conducted on 52 patients with RA treated with at least one dose of rituximab for 135.3 patient-years were included. Three treatment groups were obtained: (G1) First course and following two 1g infusions separated by 15 days; (G2) First course 2 infusions of 1g followed by 2 infusions of 500mg; (G3) First course and followed by 2 infusions of 500mg separated by 15 days. Re-treatments were administered on-demand according to the clinical activity. The retention time (Log-Rank), retreats and adverse events rates (incidence rate ratio) and treatment costs per patient-month of rituximab were analysed by groups. RESULTS: Group 2 showed a better cost-effectiveness ratio than group 1, as it was associated with a longer retention of rituximab (mean [95% CI] 65.7 [60.8 to 70.7] months vs 33.5 [22.7 to 44.3]; P<.001) and a lower rate of severe adverse events with only a slight increase in the rate of retreatment (courses/patient-year [95% CI] 1.66 [1.39 to 1.93] vs. 1.01 [0.69 to 1.34]; P=.005), and in the costs (median/patient-month, €484.89 vs. €473.45). Although group 3 was €41.20/patient-month cheaper than group 2, it was associated with a higher rate of re-treatments and shorter retention of rituximab (P<.001). CONCLUSIONS: The use of full-dose rituximab at onset, followed by reduced doses in successive courses administered on-demand retreatment may be the most cost-effective option

Eficiency of different doses of rituximab in rheumatoid arthritis. / Eficiencia de diferentes dosis de rituximab en la artritis reumatoide.

OBJECTIVE: Evaluate the effectiveness, cost and safety of rituximab in patients with rheumatoid arthritis (RA) depending on the dose used. MATERIAL AND METHODS: Retrospective observational study conducted on 52 patients with RA treated with at least one dose of rituximab for 135.3 patient-years were included. Three treatment groups were obtained: (G1) First course and following two 1g infusions separated by 15 days; (G2) First course 2 infusions of 1g followed by 2 infusions of 500mg; (G3) First course and followed by 2 infusions of 500mg separated by 15 days. Re-treatments were administered on-demand according to the clinical activity. The retention time (Log-Rank), retreats and adverse events rates (incidence rate ratio) and treatment costs per patient-month of rituximab were analysed by groups. RESULTS: Group 2 showed a better cost-effectiveness ratio than group 1, as it was associated with a longer retention of rituximab (mean [95% CI] 65.7 [60.8 to 70.7] months vs 33.5 [22.7 to 44.3]; P<.001) and a lower rate of severe adverse events with only a slight increase in the rate of retreatment (courses/patient-year [95% CI] 1.66 [1.39 to 1.93] vs. 1.01 [0.69 to 1.34]; P=.005), and in the costs (median/patient-month, €484.89 vs. €473.45). Although group 3 was €41.20/patient-month cheaper than group 2, it was associated with a higher rate of re-treatments and shorter retention of rituximab (P<.001). CONCLUSIONS: The use of full-dose rituximab at onset, followed by reduced doses in successive courses administered on-demand retreatment may be the most cost-effective option.

Reducing the need for central dual-energy X-ray absorptiometry in postmenopausal women: efficacy of a clinical algorithm including peripheral densitometry.

We evaluated the efficacy of a triage approach based on a combination of osteoporosis risk-assessment tools plus peripheral densitometry to identify low bone density accurately enough to be useful for clinical decision making in postmenopausal women. We conducted a cross-sectional diagnostic study in postmenopausal Caucasian women from primary and tertiary care. All women underwent dual-energy X-ray absorptiometric (DXA) measurement at the hip and lumbar spine and were categorized as osteoporotic or not. Additionally, patients had a nondominant heel densitometry performed with a PIXI densitometer. Four osteoporosis risk scores were tested: SCORE, ORAI, OST, and OSIRIS. All measurements were cross-blinded. We estimated the area under the curve (AUC) to predict the DXA results of 16 combinations of PIXI plus risk scores. A formula including the best combination was derived from a regression model and its predictability estimated. We included 505 women, in whom the prevalence of osteoporosis was 20 %, similar in both settings. The best algorithm was a combination of PIXI + OST + SCORE with an AUC of 0.826 (95 % CI 0.782-0.869). The proposed formula is Risk = (-12) × [PIXI + (-5)] × [OST + (-2)] × SCORE and showed little bias in the estimation (0.0016). If the formula had been implemented and the intermediate risk cutoff set at -5 to 20, the system would have saved 4,606.34 in the study year. The formula proposed, derived from previously validated risk scores plus a peripheral bone density measurement, can be used reliably in primary care to avoid unnecessary central DXA measurements in postmenopausal women.

Baseline comorbidities in patients with rheumatoid arthritis who have been prescribed biological therapy: a case control study

Objetivo. Determinar si los pacientes con artritis reumatoide (AR) a los que se les prescribe terapia biológica tienen comorbilidad diferente a los pacientes con AR a los que se les prescribe solo fármacos antirreumáticos modificadores de la enfermedad (FAME). Entender la asociación de comorbilidad con otras variables y con multimorbilidad. Métodos. Estudio observacional de casos y controles, incluyó 114 pacientes con AR a los que se les prescribió terapia biológica, y un grupo control de 163 pacientes emparejados por sexo y edad a los que solo se les había prescrito FAME. Se recogieron datos previos y actuales sobre actividad de enfermedad, comorbilidad y tratamientos. Se realizó análisis de regresión bivariante y multivariante. Resultados. Los pacientes a los que se les prescribió terapia biológica tenían: peor control de la enfermedad, recibieron más FAME y glucocorticoides y se habían sometido a más artroplastias en comparación con el grupo control. Sin embargo, los factores de riesgo cardiovascular y la frecuencia de comorbilidad fueron similares entre casos y controles. Las comorbilidades más frecuentes fueron: hipercolesterolemia (33%), hipertensión (27%), obesidad (26%), y trastornos respiratorios (16%), tiroideos(13%) y gastrointestinales (10%). La incidencia de enfermedad cardiovascular es baja (2%). Solo el 29% de los pacientes tenían multimorbilidad. Se observó asociación bivariante entre edad, diagnóstico tardío, reemplazos articulares y HAQ, con comorbilidad. También se observaron correlaciones entre índice de Charlson y edad, la cirugía reconstructiva, actividad de la enfermedad y HAQ. Cuando se aplican los modelos de regresión Log binario, solo la edad se mantuvo asociada significativamente con comorbilidad y multimorbilidad (hazard ratio 1,8; intervalo de confianza al 95% 1,05-1,12; p<0,0005). Conclusión. Los pacientes con AR con terapia biológica tienen comorbilidad equivalente a los tratados solo con FAME. La edad es el principal factor predictivo de comorbilidad en estos pacientes (AU)

Aim: To determine whether rheumatoid arthritis (RA) patients who have been prescribed biological agents exhibit a different comorbidity burden than RA patients who take disease-modifying antirheumatic drugs (DMARDs) alone, and to understand the association between comorbidity and other variables, as well as the association between comorbidity and multimorbidity. Methods: This observational case–control study included 114 RA patients treated with biological agents and a control group comprising 163 sex- and age-matched RA patients treated with DMARDs only. Current and previous data regarding the patients’ disease activity, comorbidities, and treatments were collected. The data were analysed using bivariate and multivariate regression models. Results: The patients who were prescribed biological agents exhibited poorer disease control, received more DMARDs and steroids, and underwent more total joint arthroplasties compared with the patients in the control group. However, the risk factors for cardiovascular disease and the comorbidity frequency were similar between cases and controls. The most prevalent comorbidities were hypertension, obesity, and respiratory, thyroid, and upper gastrointestinal disorders. The incidence of cardiovascular disease was low, and only 29% of the patients exhibited multimorbidities. A bivariate association of age, late diagnosis, joint replacements and a high score on the health assessment questionnaire score (HAQ) with comorbidity was observed. There were also correlations between the Charlson index and age, joint reconstructive surgery, disease activity (DAS28), and HAQ score. However, when binary logarithmic regression models were applied, only patient age remained significantly associated with comorbidity and multimorbidity [hazard ratio, 1.08; 95% confidence interval, 1.05–1.12; p < 0.0005]. Conclusion: RA patients taking biological drugs have a comorbidity burden equivalent to those treated with DMARDs alone. Age is the main predictive factor of comorbidity in these patients (AU)

Baseline comorbidities in patients with rheumatoid arthritis who have been prescribed biological therapy: a case control study.

AIM: To determine whether rheumatoid arthritis (RA) patients who have been prescribed biological agents exhibit a different comorbidity burden than RA patients who take disease-modifying antirheumatic drugs (DMARDs) alone, and to understand the association between comorbidity and other variables, as well as the association between comorbidity and multimorbidity. METHODS: This observational case-control study included 114 RA patients treated with biological agents and a control group comprising 163 sex- and age-matched RA patients treated with DMARDs only. Current and previous data regarding the patients' disease activity, comorbidities, and treatments were collected. The data were analysed using bivariate and multivariate regression models. RESULTS: The patients who were prescribed biological agents exhibited poorer disease control, received more DMARDs and steroids, and underwent more total joint arthroplasties compared with the patients in the control group. However, the risk factors for cardiovascular disease and the comorbidity frequency were similar between cases and controls. The most prevalent comorbidities were hypertension, obesity, and respiratory, thyroid, and upper gastrointestinal disorders. The incidence of cardiovascular disease was low, and only 29% of the patients exhibited multimorbidities. A bivariate association of age, late diagnosis, joint replacements and a high score on the health assessment questionnaire score (HAQ) with comorbidity was observed. There were also correlations between the Charlson index and age, joint reconstructive surgery, disease activity (DAS28), and HAQ score. However, when binary logarithmic regression models were applied, only patient age remained significantly associated with comorbidity and multimorbidity [hazard ratio, 1.08; 95% confidence interval, 1.05-1.12; p<0.0005]. CONCLUSION: RA patients taking biological drugs have a comorbidity burden equivalent to those treated with DMARDs alone. Age is the main predictive factor of comorbidity in these patients.