The purpose of this study is to determine wether pirfenidone is safe and effective in the treatment of pulmonary fibrosis with anti-myeloperoxydase (MPO) antibodies or pulmonary fibrosis with anti-MPO associated vasculitis.

Pulmonary fibrosis can be associated with Anti-Neutrophil Cytoplasmic Antibody (ANCA) directed against MPO or with anti-MPO associated vasculitis, leading to increased disability and poor prognosis. The pathophysiology of this association remains unclear. Conventional therapies used for the treatment of vasculitis manifestations are often disappointing for the treatment of pulmonary fibrosis. The main cause of death in patients with anti-MPO ANCA associated vasculitis and associated pulmonary fibrosis is the progression of pulmonary fibrosis. No treatment has demonstrated efficacy to stabilize or improve pulmonary fibrosis associated with anti-MPO associated vasculitis.

Previous studies showed that Pirfenidone improves survival and pulmonary function in patients with idiopathic pulmonary fibrosis (IPF) and that Pirfenidone treatment is safe and well tolerated in IPF. Patients with anti-MPO associated vasculitis (or anti-MPO antibodies without vasculitis) and associated pulmonary fibrosis might benefit from the use of Pirfenidone. However, the efficacy and safety of pirfenidone in patients with anti-MPO associated vasculitis and associated pulmonary fibrosis has not been evaluated. This study was designed to assess the efficacy and safety of pirfenidone in patients with pulmonary fibrosis and anti-MPO ANCA associated vasculitis or anti-MPO antibodies without vasculitis.

Inclusion Criteria:

• Age > 18 years
• Presence of anti-MPO antibody (ELISA) at inclusion or during pulmonary fibrosis follow-up and/or diagnosis of anti-MPO associated vasculitis according to the 2012 Revised International Chapel Hill Consensus Conference definitions
• Definite or possible Usual Interstitial Pneumonia or Non Specific Interstitial Pneumonia based on high-resolution computed tomography
• Presence of pulmonary fibrosis, defined as a range of 50 to 90% of the %FVC and a range of 30 to 90% of the %DLCO
• Pulmonary fibrosis refractory (according to the investigator's judgment) to a conventional regimen used for anti-MPO associated vasculitis when a treatment against vasculitis has been used
• Have the ability to understand the requirements of the study, provide written informed consent (including consent for the use and disclosure of research-related health information) and comply with the study protocol procedures (including required study visits)
• Have affiliation with a mode of social security (profit our being entitled).

Exclusion Criteria:

• Other type of systemic vasculitis;
• Active vasculitis defined by Birmingham Vasculitis Activity Score >3 (BVAS) ;
• Contraindication to Pirfenidone;
• Unable to perform pulmonary function test (PFT);
• Pregnancy or lactation. Women of childbearing capacity are required to have a negative serum pregnancy test before treatment and must agree to maintain highly effective contraception by practicing abstinence or by using an effective method of birth control from the date of consent through the end of the study : implants of levonorgestrel; injectable progesterone; any intrauterine device (IUD) with a documented failure rate of less than 1% per year; oral contraceptives (either combined or progesterone only); double barrier method (condom, cervical cap or diaphragm with spermicidal agent); transdermal contraceptive patch; male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for the female subject;
• Any of the following liver function test criteria above specified limits: total bilirubin above 1,5 times the upper limit of normal (ULN), excluding patients with Gilbert's syndrome; aspartate (AST)/Glutamate Oxaloacétique Transaminase (SGOT) or alanine aminotransferase (ALT)/Glutamate Pyruvate Transaminase (SGPT), (AST/SGOT or ALT/SGPT) >3 × ULN; alkaline phosphatase >2.5 × ULN;
• Creatinine clearance (CrCl<30) mL/min, calculated using the Cockcroft-Gault formula at screening
• Current treatment with Nintedanib or past treatment with Nintedanib in the last 12 months;
• Current treatment with Fluvoxamine or past treatment with Fluvoxamine in the last 28 days before screening
• Prior use of Pirfenidone or known hypersensitivity to any of the components of study treatment;
• Expected to receive a lung transplant within 1 year from randomization or, on a lung transplant waiting list at randomization;
• Associated connective tissue disease (such as systemic sclerosis).;
• Electrocardiogram (ECG), with a heart-rate-corrected QT interval (corrected using Fridericia's formula, QTcF) ≥ 500 ms at Screening, or a family or personal history of long QT syndrome;
• Treatment with Cyclophosphamide in the last 3 months;
• Current smoking or past smoking in the last 3 months.