This project will address rare immune mediated inflammatory diseases (IMIDs) involving the lungs, i.e. interstitial pneumonitis (IP). The main objective of this study is to assess the effects of rituximab (RTX) as a rescue therapy for progressive IMID-IP patients. The primary study parameter is pulmonary function.

The secondary objectives are to explore the application of imaging with radiolabeled RTX as early predictor for efficacy of RTX, to study the effects of RTX treatment on quality of life, and to further elucidate the pathophysiology of IMID-IP by analyzing biochemical markers.

Inclusion Criteria:

In order to be eligible to participate in the study, subjects must meet all of the following criteria:

• Age 18 to 70 years
• No previous therapy with rituximab
• At least 2 pulmonary function tests within past 6 months
• Diagnosis of co-existing IMID and a severe and / or progressive IP characterized by 3 out of the following items:
• Respiratory symptoms consistent with interstitial lung disease
• Diagnosis of usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), organizing pneumonia (OP) or a mixed form of UIP / NSIP / OP by either of the following:
• Open or video-assisted thoracic surgery (VATS) lung biopsy showing definite or probable UIP / NSIP / OP
• High Resolution Computer Tomography (HRCT) scan showing definite or probable UIP/NSIP/OP/mixed
• Forced Vital Capacity (FVC) < 50% predicted and/or diffusing capacity of the lung for carbon monoxide (DLCO) < 40% predicted or worsening of lung function as demonstrated by any one of the following within the past year:
• > 10% decrease in FVC
• > 15% decrease in DLCO
• Therapy resistance to 1st (corticosteroids) and 2nd line therapy(cyclophosphamide or azathioprine)

Exclusion Criteria:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

• Residual volume >120% predicted at screening
• DLCO <25% of predicted value at screening + resting Oxygen Saturation (SAO2) without external oxygen <90%
• History of unstable or deteriorating cardiac or neurological disease
• Pregnancy or lactation
• Hematology lower than specified limits (leucocytes)
• Positive HIV, hepatitis B or C serology
• Pre-existing conditions which lead to a life expectancy of less than 6 months
• Receipt of any vaccine, particularly live viral vaccines, within 4 weeks before first rituximab dose
• Hypersensitivity for murine proteins

NOTE:

• Fever (>37,9 °C) at presentation is reason to delay therapy by 1 week
• Evidence of active infection is reason to postpone rituximab treatment until no further signs of active infection
• Severe renal impairment is not a contraindication for rituximab therapy, however, if patients (might) require dialysis frequently they will be excluded from the study group