Targeted therapies in interstitial lung disease secondary to systemic autoimmune rheumatic disease. Current status and future development

Autoimmune rheumatic diseases (ARD) are characterized by systemic manifestations and multiple organ involvement, including the lung. Interstitial Lung Disease (ILD) is a cardinal manifestation of lung involvement in patients with ARD and is associated with significant morbidity and mortality. Corticosteroids and immunosuppressive drugs are used as first –line treatment. Targeted therapies, such as biological disease modifying antirheumatic drugs (DMARDS) and anti- fibrotic agents are new treatment options. In this review we discuss the role of targeted therapies in patients with ILD secondary to ARD. © 2020 Elsevier B.V

How can autoantibodies predict the long-term outcome of patients with interstitial lung disease? Results from a retrospective cohort study

Objectives: This study aimed to investigate whether positive serum autoantibodies (AAbs) have any impact on survival and time evolution of radiological findings and pulmonary function indices in patients with interstitial lung disease (ILD). Patients and methods: Ninety four patients with regular clinical, functional and high resolution computed tomography (HRCT) imaging follow-up for at least 12 consecutive months and complete testing for a panel of AAbs most commonly associated with ILD were enrolled in this retrospective two-center study. Eligible patients were divided into two groups based on the presence [ILD/AAb(+)] (n = 69) or absence [ILD/AAb(−)] (n = 25) of positive serum AAbs. All-cause mortality and longitudinal indicators of ILD progression such as a sustained decrease from baseline in absolute measurements of forced vital capacity (FVC) of ≥10% or single-breath diffusion capacity (DLCOSB) of ≥15% were the primary study endpoints. DLCOSB < 40% predicted on at least two consecutive measurements and progression of HRCT findings were our secondary endpoints. Kaplan–Meier (K-M) survival analysis and multivariate Cox proportional-hazards (PH) model were used to evaluate the prognostic significance of positive AAbs in the outcome of patients with ILD. Results: ILD/AAb(+) patients were predominantly female (71% vs 32%), were significantly younger (54.8 ± 14.6 vs 66.8 ± 10.1 years), and had longer duration of follow-up (78.1 ± 53.1 vs 41.6 ± 26.7 months), compared with ILD/AAb(−) patients (p <.01 for each comparison). Baseline measurements of FVC (% pred.) and DLCOSB (% pred.) did not differ significantly between the two groups. At the end of follow-up, mortality rates and the percentage of patients with a sustained FVC decrease were lower in the ILD/AAb(+) group (p <.05 for each comparison). With the exception of DLCOSB < 40% pred., ILD/AAb(+) patients had a longer median time-to-event for each of the other studied outcomes (p <.01 for each K-M analysis). In addition, Cox PH models adjusted for age, smoking status, baseline pulmonary function tests and morphological pattern of ILD remained statistically significant in favor of the ILD/AAb(+) group (p <.05 for each comparison). Conclusions: AAb(+) patients with ILD seem to have a more favorable prognosis regarding all-cause mortality, long-term deterioration in lung function parameters and progression of HRCT findings than their AAb (−) counterparts. © 2018 Elsevier B.V

Long-term clinical effects of interferon gamma-1b and colchicine in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia is a deadly disease with no effective treatment. The purpose of this randomised prospective multicentric study was to characterise the clinical effects of interferon gamma (IFN-γ) 1b administered subcutaneously thrice weekly versus colchicine for 2 yrs. This study had no pre-specified end-points. Fifty consecutive IPF patients were randomised. Patients with mild-to-moderate IPF were eligible for the study if they had histologically proven IPF, or, in the absence of surgical biopsy, fulfilled the European Respiratory Society/American Thoracic Society criteria. In the intent-to-treat population, five out of 32 (15.6%) IFN-γ-1b patients and seven out of 18 (38.8%) colchicine patients died after a median follow-up period of 25 months Patients treated with IFN-γ 1b showed a better outcome after 2 yrs of therapy, and fewer symptoms, as assessed using the St George's Respiratory Questionnaire, after 12 months of therapy. Also, the IFN-γ-1b group exhibited a higher forced vital capacity (percentage of the predicted value) after 24 months of treatment. No significant differences were detected in resting arterial oxygen tension, total lung capacity (% pred), transfer factor of the lung for carbon monoxide (% pred) and high-resolution computed tomographic scoring between the two treatment groups. These data suggest that long-term treatment with interferon gamma 1b may improve survival and outcome in patients with mild-to-moderate idiopathic pulmonary fibrosis. Further studies are needed to verify these results. Copyright ©ERS Journals Ltd 2006