Rituximab in Interstitial Pneumonitis

• Rituximab (Drug): 2 times 1000mg dose at 14 days interval treatment
• Zr-89-rituximab immuno PET/CT (Radiation), also known as Immuno PET: Immuno labeled PET/CT of the lungs

Primary outcomes

• Pulmonary function (VC, DLCO) [6 - 12 months]: establish a change from the downward decline in pulmonary function (absolute values and values predicted of VC = Vital Capacity and DLCO = Diffusion capacity of Lung Carbon monoxide)

Secondary outcomes

• Zr-89 Immuno PET [3, 6 days after injection]: This is a scan with radiolabelled rituximab (visualizing rituximab activity in the lungs). Calculated activity (SUV) in the lungs vs. blood pool vs liver vs.control group (n=15) is measured with standard deviation. The amount of uptake in the lungs and the clinical response of patients will be correlated to determine a correlation.

Sex: All, ages: 18 Years to 70 Years

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

• Results publication: Adams H, van de Garde EMW, Vugts DJ, Grutters JC, Oyen WJG, Keijsers RG. [89Zr]-immuno-PET prediction of response to rituximab treatment in patients with therapy refractory interstitial pneumonitis: a phase 2 trial. Eur J Nucl Med Mol Imaging. 2023 Jun;50(7):1929-1939. doi: 10.1007/s00259-023-06143-1. Epub 2023 Feb 24. PMID 36826476

• J C Grutters, MD, PhD, Principal investigator, St. Antonius Hospital