The cause(s) of idiopathic pulmonary fibrosis (IPF) remain unknown, as well as the factors that result in the progression of this disease. No established medical treatments have yet been shown to benefit patients with this disease, and IPF continues to have a worse prognosis than many common malignancies. Recent findings of our research group, as well as others, show that autoantibodies are associated with IPF progression. Results of an early ongoing pilot study further indicate that specific treatments aimed at reducing pre-existing autoantibodies and/or minimizing their future production improve lung function among very ill IPF patients who are having disease exacerbations. We hypothesize that antibody-mediated autoimmunity can play an important role in IPF progression. The presence of autoimmunity could explain the refractoriness of this disease to current therapy, since many autoantibody lung diseases are resistant to treatment with corticosteroids. However, focused treatments targeted at autoantibodies or the lymphocytes that produce these immunoglobulins often have greater efficacy for these diseases than steroids or other nonspecific therapies. Accordingly, we propose here a multicenter, randomized, double-blind, placebo-controlled Phase II clinical trial to explore the efficacy and safety of rituximab (anti-CD20 monoclonal antibody) vs. placebo, among patients with IPF. Fifty-eight (58) ambulatory IPF subjects at four participating U.S. medical centers will be randomized (1:1) to either the experimental arm (rituximab) or placebo. The primary end-point is a global assessment of circulating autoantibodies. Secondary end-points are measures of a specific autoantibody that is associated with clinical progression (anti-heat shock protein 70), as well as a measure of lung function (forced vital capacity), and adverse event rates. We anticipate the novel experimental treatment will show targeted efficacy for reduction of autoantibodies, a favorable safety profile, and possibly stabilization of lung function. Results of these investigations will establish the efficacy and pharmacokinetics of rituximab treatment in IPF patients. Ultimately these studies could challenge current paradigms of IPF pathogenesis, and substantially alter treatment approaches to patients afflicted with this morbid, refractory disease.

Public Health Relevance

Idiopathic pulmonary fibrosis (IPF) is a dreaded, usually fatal lung disease of older adults. No medical treatments seem effective. We have found evidence that autoimmunity appears to be involved in IPF, in which the patient's own immune system attacks the lung. We believe the experimental treatment of this trial that targets this autoimmune process will ultimately be shown to be effective therapy for these patients. (End of Abstract)

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZHL1)
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Eu, Jerry Pc
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University of Pittsburgh
Internal Medicine/Medicine
Schools of Medicine
United States
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Li, Fu Jun; Surolia, Ranu; Li, Huashi et al. (2017) Autoimmunity to Vimentin Is Associated with Outcomes of Patients with Idiopathic Pulmonary Fibrosis. J Immunol 199:1596-1605
Donahoe, Michael; Valentine, Vincent G; Chien, Nydia et al. (2015) Autoantibody-Targeted Treatments for Acute Exacerbations of Idiopathic Pulmonary Fibrosis. PLoS One 10:e0127771
Vuga, Louis J; Tedrow, John R; Pandit, Kusum V et al. (2014) C-X-C motif chemokine 13 (CXCL13) is a prognostic biomarker of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 189:966-74
Thannickal, Victor J; Zhou, Yong; Gaggar, Amit et al. (2014) Fibrosis: ultimate and proximate causes. J Clin Invest 124:4673-7