The main objective of the EvER-ILD2 study is to evaluate the efficacy on lung function at 6 months of one course rituximab (2 infusions) comparatively to one course of placebo (2 infusions) in a broad range of progressive ILD patients with inflammatory component.

Inclusion Criteria:

1. Patients ≥ 18 years old

2. Who meet at least one of the following criteria for worsening ILD within 24 months:

   1. a relative decline in the FVC of >= 10% of the predicted value
   2. a relative decrease in the FVC of >=5 to 10% of the predicted value AND i) worsening respiratory symptoms OR ii) an increased extent of ILD on high-resolution CT OR iii) a relative decrease in the DLCO of >= 15% of the predicted value.
   3. worsening of respiratory symptoms AND an increased extent of ILD on high-resolution CT

3. AND presence of an inflammatory component defined by

   1. a previous histological pattern with lymphocyte infiltrations distant from pulmonary fibrosis to suggest an inflammatory component on pulmonary sample (for example: interstitial lymphoid aggregates with germinal centers, diffuse lympho-plasmocytic infiltrations, granulomas, giant cells or centrilobular inflammation…)
   2. OR a previous alveolar lymphocytosis >20% on Bronchoalveolar lavage fluid (BALF)

4. Subjects covered by the French social security system

5. Written informed consent obtained from subject

6. Ability for subject to comply with the requirements of the study

Exclusion Criteria:

1. Known diagnosis of significant respiratory disorders (asthma, tuberculosis, aspergillosis, cystic fibrosis, idiopathic pulmonary fibrosis (IPF), Connective Tissue Diseases-ILD, sarcoidosis, desquamative interstitial pneumonia, pulmonary hypertension (PAMp > 30mmHg))) or of significant severe heart failure.
2. Concomitant medical or surgical disease, clinically significant as considered by the investigator, serious or unstable, acute or chronically progressive, or any condition that could affect the safety of the patient, in the opinion of the investigator including cardiomyopathy or heart failure.
3. Patient who can not walk more than 100 meters at 6-minutes walk test
4. HRCT profile of typical usual interstitial pneumonia (UIP)
5. Histological model of typical NSIP or definitive UIP
6. Initiation of a new therapy or with interruption/modification of therapy dosage within 6 weeks prior to visit 1
7. Patient who has already received a rituximab-based treatment line
8. Known hypersensitivity to rituximab, to murine proteins or other excipients or sulfonamide antibiotics.
9. Treatment with monoclonal antibodies (such as, but not limited to, etanercept, adalimumab, efalizumab, infliximab, golimumab, certolizumab) within 6 months (if 5 half-lives ≤ 6 months) prior to inclusion.
10. Patients on a lung transplant list
11. Pregnant or breastfeeding women, or women of childbearing age not using a reliable method of contraception during the study and for 12 months following the end of the study treatment.
12. Patients at high risk of infectious complications: Human Immunodeficiency Virus (HIV) positive or other known immunodeficiency syndromes, hepatitis B and C (HBV, HCV), coronavirus disease (within 3 month) or other known viral infection, infection requiring anti-infective treatment within 4 weeks of inclusion.
13. Patients with incomplete anti-severe acute respiratory syndrome coronavirus 2 vaccine regimen (according to current recommendations) and in this case who has not receive a treatment with therapeutic antibodies anti-SARSCov2 (ex: tixagévimab/cilgavimab)
14. Patient under judicial protection, deprivation of liberty
15. Participation in other interventional research with an investigational drug or medical device.