Immunosuppressive Therapy for Usual Interstitial Pneumonia in Autoimmune Rheumatic Diseases: A Review

Abstract

Usual Interstitial Pneumonia (UIP) is the most severe radiological/histological pattern of Interstitial Lung Disease (ILD). It is typical of Idiopathic Pulmonary Fibrosis (IPF), but is also frequently described in Autoimmune Rheumatic Diseases (ARDs), sharing with IPF common risk factors, genetic backgrounds, and in some cases, disease progression and prognosis. Following the results of the PANTHER study, immunosuppressive drugs are now not recommended for the treatment of IPF; however, their use for the treatment of UIP secondary to ARDs is still under debate. The aim of this review is to summarize existing knowledge on the clinical presentation of autoimmune UIP and its treatment with immunosuppressive drugs. We searched PubMed for English language clinical trials and studies on treatment of ARDs-ILD, looking for specific treatments of UIP-ARDs. The available clinical trials rarely stratify patients by ILD pattern, and clinical studies generally lack a comparison with a placebo group. In Systemic Sclerosis, UIP patients showed a non-significant trend of worsening under immunosuppression. On the contrary, in Interstitial Pneumonia with Autoimmune Features and, above all, Rheumatoid Arthritis, immunosuppressive treatment produced promising results in the management of UIP patients. In conclusion, the current evidence about the immunosuppressive treatment of UIP-ARDs is limited and conflicting. There is an urgent need to adequately assess this topic with specific clinical trials, as has already been performed for IPF. The possibility should be considered that different ARDs can respond differently to immunosuppression. Finally, a wider use of histological samples could produce valuable information from a diagnostic, therapeutic, and research point of view.

Keywords: Sjögren’s syndrome; anti-synthetase syndrome; fibrosis; idiopathic inflammatory myopathies; idiopathic pulmonary fibrosis; interstitial lung disease; rheumatoid arthritis; systemic sclerosis; treatment; usual interstitial pneumonia.

Figure 1

Schematic of pathogenesis of lung fibrosis. AEC: Alveolar Epithelial Cell; CTGF: Connective Tissue Growth Factor; IL-8: Interleukin 8; TGFβ: Transforming Growth Factor β.

Figure 2

Progression of respiratory trials compared with progress in knowledge about ACPA autoantibodies in Rheumatoid Arthritis. Figure Caption: (1): Nienhuis RL et al., Ann Rheum Dis 1964 [29]; (2): Demendts N et al., New Eng J Med 2005 [21]; (3): Sebbag N et al., J Clin Invest 1995 [30]; (4): Schellenkens GA et al., J Clin Invest 1998 [31]; (5): Schellenkens GA et al., Arthritis Rheum 2000 [32]; (6): Coenen D et al., Clin Chem 2007 [33]; (7): PANTHER Study, New Eng J Med 2012 [22]; (8): Aletaha D et al., Ann Rheum Dis 2010 [34].