nintedanib and Arthritis--Rheumatoid

To provide an overview of recent studies that could be helpful in a better understanding of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and to facilitate the clinical management of this severe complication of RA.. The advances in deciphering the genetic architecture of RA-ILD support the hypothesis of RA-ILD as a complex disease with a complex phenotype encompassing at least the usual interstitial pneumonia (UIP) high-resolution CT pattern and non-UIP. Genetics studies have provided evidence for a shared genetic background in idiopathic pulmonary fibrosis (IPF) and RA-ILD, and more specifically RA-UIP, a disease with high morbidity and mortality. These findings support the rationale for common pathogenic pathways opening new avenues for future intervention in RA-ILD, notably with - drugs that proved active in IPF. In agreement, a recent controlled trial suggests efficacy of nintedanib, an antifibrotic drug, in patients with progressive lung fibrosis, including RA-ILD. However, there is a substantial gap in RA-ILD treatment, notably evaluating the effect of the RA treatments on the ILD course because of no controlled trial yet.. The phenotypical, environmental, and genetic similarities between IPF and RA-ILD have led to a better understanding of the underlying pathogenesis of RA-ILD. Despite the identification of several biomarkers and useful screening tools, several questions remain unanswered regarding the identification of patients with RA at increased risk of ILD and risk of progression. Other substantial gaps are the lack of recommendations for how high-risk patients should be screened and which specific therapeutic strategy should be initiated. International collaborative efforts are needed to address these issues and develop specific recommendations for RA-ILD.

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Biomarkers; Disease Progression; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Lung Diseases, Interstitial; Phenotype; Prognosis; Protein Kinase Inhibitors; Pulmonary Fibrosis; Tomography, X-Ray Computed

Interstitial lung disease (ILD) is a common manifestation of systemic autoimmune diseases and a leading cause of death in these patients. A proportion of patients with autoimmune ILDs develop a progressive fibrosing form of ILD, characterized by increasing fibrosis on high-resolution computed tomography, worsening of lung function, and early mortality. Autoimmune disease-related ILDs have a variable clinical course and not all patients will require treatment, but all patients should be monitored for signs of progression. Apart from systemic sclerosis-associated ILD, the limited evidence to support the efficacy of immunosuppression as a treatment for ILDs is based mainly on small retrospective series and expert opinion. Non-clinical data suggest that there are commonalities in the mechanisms that drive progressive fibrosis in ILDs with an immunological trigger as in other forms of progressive fibrosing ILD. This suggests that nintedanib and pirfenidone, drugs known to slow disease progression in patients with idiopathic pulmonary fibrosis, may also slow the progression of ILD associated with systemic autoimmune diseases. In the SENSCIS® trial, nintedanib reduced the rate of ILD progression in patients with systemic sclerosis-associated ILD. The results of other large clinical trials will provide further insights into the role of anti-fibrotic therapies in the treatment of autoimmune disease-related ILDs.

Topics: Arthritis, Rheumatoid; Autoimmune Diseases; Clinical Trials as Topic; Disease Progression; Humans; Immunosuppression Therapy; Indoles; Kaplan-Meier Estimate; Lung; Lung Diseases, Interstitial; Phenotype; Pulmonary Fibrosis; Pyridones; Risk Factors; Tomography, X-Ray Computed

Interstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA). Nintedanib has been approved for the treatment of idiopathic pulmonary fibrosis. Herein, we described the case of an 87-year-old woman treated with Janus kinase inhibitor (JAKi). Chest computed tomography revealed increased honeycombing; she was administered nintedanib while continuing RA treatment. The combination treatment (JAKi and nintedanib) controlled the RA disease activity without ILD deterioration. This case shows the potential of combination treatment with JAKi and nintedanib for the prevention of worsening of disease activity in RA and ILD.

Topics: Aged, 80 and over; Arthritis, Rheumatoid; Female; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Janus Kinase Inhibitors; Lung Diseases, Interstitial; Treatment Outcome

Nintedanib is a multi-tyrosine kinase inhibitor widely used to treat progressive fibrosing interstitial lung diseases because it slows the reduction in forced vital capacity. However, the prognosis for patients treated with nintedanib remains poor. To improve nintedanib treatment, we examined the effects of nintedanib on gene expression in the lungs of induced-rheumatoid arthritis-associated interstitial lung disease model mice, which develop rheumatoid arthritis and subsequent pulmonary fibrosis. Using next-generation sequencing, we identified 27 upregulated and 130 downregulated genes in the lungs of these mice after treatment with nintedanib. The differentially expressed genes included mucin 5B and heat shock protein 70 family genes, which are related to interstitial lung diseases, as well as genes associated with extracellular components, particularly the myocardial architecture, suggesting unanticipated effects of nintedanib. Of the genes upregulated in the nintedanib-treated lung, expression of regulatory factor X2, which is suspected to be involved in cilia movement, and bone morphogenetic protein receptor type 2, which is involved in the pathology of pulmonary hypertension, was detected by immunohistochemistry and RNA in situ hybridization in peripheral airway epithelium and alveolar cells. Thus, the present findings indicate a set of genes whose expression alteration potentially underlies the effects of nintedanib on pulmonary fibrosis. It is expected that these findings will contribute to the development of improved nintedanib strategies for the treatment of progressive fibrosing interstitial lung diseases.

Topics: Animals; Arthritis, Rheumatoid; Gene Expression; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Lung; Lung Diseases, Interstitial; Mice; Protein Kinase Inhibitors

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Connective Tissue Diseases; Disease Progression; Humans; Indoles; Interleukin-6; Lung Diseases, Interstitial; Methotrexate; Prevalence; Protein Kinase Inhibitors; Pulmonary Fibrosis; Randomized Controlled Trials as Topic; Scleroderma, Systemic; Vital Capacity

Topics: Aged; Antirheumatic Agents; Arthritis, Rheumatoid; Female; Humans; Indoles; Lung Diseases, Interstitial; Male; Middle Aged

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Connective Tissue Diseases; Dermatomyositis; Humans; Indoles; Ireland; Lung Diseases, Interstitial; Protein Kinase Inhibitors; Rheumatology; Scleroderma, Systemic; Sjogren's Syndrome; Societies, Medical; United Kingdom; United States