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

Abstract

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.

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

“…These results are similar or even superior to those observed in other cohorts of patients with ILD-SAI [5,[40][41][42]. This improvement is probably associated with increased use of specific immunosuppressants and biologics [43,44]. Furthermore, the predominance of patients with RA (followed by SS and IM) reflects the prevalence reported for each of these diseases elsewhere [45].…”

Decision-Making Strategy for the Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD)

“…Of the patients without respiratory restriction at the initial diagnosis, about 10% of them had developed severe restrictive disorder over the 5 years [29]. Mena-Vázquez et al reported in 2021 that 19.8% of RA-ILD patients had experienced progression (worsening of FVC of >10% or DLCO of >15% and radiological progression) over the 5 years from their ILD diagnosis [30]. These patients were classified as having progressive fibrosing ILD (PF-ILD) [31,32].…”

“…The independent predictors of worsening of RA-ILD were reported to be the usual interstitial pneumonia (UIP) pattern, lowered FVC (e.g., <80%), cigarette smoking, and higher anticitrullinated protein antibody titers [20,25,30,33]. Mena-Vázquez et al reported that treatment with abatacept (ABT) as a synthetic analog of CTLA-4Ig, tocilizumab (TCZ) as an interleukin-6 inhibitor (IL-6i), and rituximab (RTX) as an anti-CD20 chimeric antibody was associated with predictors of stabilized pulmonary function [30]. Factors significantly related to mortality in RA were male sex, older age, having ILD, and higher articular activity [5].…”

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

“…However, one meta-analysis did not report a higher frequency of respiratory adverse effects [14]. As for biologic DMARDS (bDMARDs), the available evidence-based mainly on cross-sectional and retrospective studies-suggests that rituximab and abatacept could be safe for CTD-ILD treatment [6,[15][16][17][18][19][20][21][22]. Tocilizumab has also been suggested to be effective in preserving lung function in SS [23].…”

“…However, some recent retrospective studies suggest that it could be an alternative treatment for patients with CTD-ILD, even in cases that prove refractory to conventional immunosuppressants [6,21,[26][27][28]. Therefore, based on a multicenter registry study of patients with CTD-ILD [21,22], we prospectively evaluated the use of rituximab with the following objectives: (1) to report on the efficacy and safety profile of rituximab in different CTD-ILDs; and (2) to identify risk factors that help to predict progression and mortality in patients treated with rituximab.…”