Autoantibody Reduction for Acute Exacerbations of Idiopathic Pulmonary Fibrosis

Inclusion Criteria

• Age between 40-85 years old.
• A diagnosis of IPF that fulfills ATS/ERS Consensus Criteria.1
• Worsening or new development of dyspnea or hypoxemia within the last 30 days.
• Ground-glass abnormality and/or consolidation superimposed on a reticular or honeycomb usual interstitial pneumonitis (UIP) pattern on locally read chest CT scan.
• Ability and willingness to give informed consent (no surrogates) and adhere to study requirements.

Exclusion Criteria

• Diagnoses of current infection per clinical or microbial assessments.
• Diagnoses of an additional or alternative etiology for respiratory dysfunction based upon clinical assessment, including congestive heart failure, sepsis, thromboembolism, etc.
• History or serologic evidence of hepatitis B or C infection.
• Coagulopathy, defined as a International Normalized Ratio (INR) >1.6, partial thromboplastin time (PTT) > 2x control, fibrinogen 160 mm Hg and diastolic BP >100 mm Hg) that would contraindicate use of corticosteroids.
• Hemodynamic instability, defined as an inotrope or vasopressor requirement.
• History of reaction to blood products or murine-derived products or prior rituximab use.
• History of malignancy, excluding basal or squamous cell skin cancer and low-risk prostate cancer, the latter defined as stage T1 or T2a, with prostate specific antigen (PSA) less than 10 ng/dl. The experimental treatments are not known to promote cancer progression, and these criteria are within current guidelines.
• Unwillingness to accept blood product transfusion.
• Diagnosis of major comorbidities expected to interfere with study participation.
• Treatment for >14 days within the preceding month with >20 mg. prednisone (or equivalent) or any treatment during the last month with a cellular immuno-suppressant (e.g., cyclophosphamide, methotrexate, calcineurin inhibitors, mycophenolate, azathioprine, etc.). An exception will be made if the patient has a bronchoalveolar lavage (BAL) negative for pathogens.
• Current treatment with an angiotensin converting enzyme inhibitor that cannot be discontinued and/or substituted (to obviate hemodynamic complications during TPE).
• Concurrent participation in other experimental trials.
• Fertile females who do not agree to contraception or abstinence, or have a positive pregnancy test (urine or blood). IPF is a disease of older adults, and male predominant, so this will not be a frequent consideration.
• Presence of positive (abnormal) classical autoimmune tests: anti-nuclear antibody (ANA), rheumatoid factor (RF), Anti- Sjögren's-syndrome-related antigen (SSA) , and Anti-Cyclic Citrullinated Peptide (CCP). This criterion will eliminate patients with confounding classical autoimmune syndromes. Many IPF patients will have already had these tests, which are standard of practice (SOP) at many IPF centers, and these prior results will suffice if the tests were performed within the last year. Otherwise, these tests need to be performed prior to enrollment and they can usually be procured in 1-2 days. Based on experience, we anticipate ~10% of patients who fulfill all other IPF criteria will nonetheless be positive for one of these classical autoantibody tests.
• IgA deficiency (IgA level <7 mg/dL)- to preclude IVIG reactions.