Rituximab and Abatacept Effectiveness in Differential Treatment of Interstitial Lymphocytic Lung Disease in Children With Primary Immunodeficiencies.

Study Overview
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Brief Summary
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The rationale for this retrospective study is to evaluate the efficacy and safety of abatacept and rituximab treatment of ILLD in a cohort of pediatric patients with different forms of PID, who received one of the two therapy regimens predominantly based on the lesions histopathology.

Detailed Description
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Primary immunodeficiencies (PID) represent a heterogeneous group of more than 400 inherited conditions with associated immune dysfunctions. Though severe recurrent/chronic infections are the main cause of mortality and morbidity in PID, immune dysregulation manifesting with oncological and autoimmune or autoinflammatory conditions involving various organs and systems have been the focus of research in the recent years. The interstitial lymphocytic lung disease (ILLD) is one of the recently characterized non-malignant PID complications. Immune dysregulation in ILLD causes reactive bronchi-associated lymphoid tissue (BALT) hyperplasia that manifests in several pathomorphological forms: follicular bronchiolitis (FB), nodular lymphoid hyperplasia (NLH), and lymphocytic interstitial pneumonia (LIP). Treatment of ILLD patients with various immunosuppressive drugs leads to inconsistent results ranging from partial\transient effect to no effect at all and has been often associated with adverse effects and an increase in infections' rate. Therefore there is a need for targeted therapy of ILLD. In small cohorts of adult PID patients rituximab in combination with azathioprine proved to be effective. Yet, the reports are scarce and there is currently no consensus on ILLD treatment, especially in children. The study will collect and analyze information on the effectiveness and safety of ILLD monotherapy with rituximab or abatacept, chosen predominantly based on the pathomorphological characteristics of lymphoid infiltration, as well as genetic defects, in a cohort of pediatric patients with PID.

Official Title
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Retrospective Chart Review of Children With Primary Immunodeficiencies (PID) Who Received Targeted Therapy of Interstitial Lymphocytic Lung Disease (ILLD) With Abatacept or Rituximab.

Conditions
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Interstitial Lymphocytic Lung Disease

Intervention / Treatment
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* Drug: Rituximab
* Drug: Abatacept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological and/or radiological diagnosis of ILLD. Treatment with rituximab or abatacept for at least 12 months. No signs of ongoing infectious pulmonary process at the start of the treatment. Regular IG substitution with trough IgG levels > 5g/l. Exclusion criteria are nonadherence to therapy.

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| group 1(rituximab)<br> | Drug: Rituximab<br>* 375 mg/m2 as 4 weekly consecutive i.v. infusions with subsequent infusions of 375 mg/m2 performed every 3 months for 12 months.<br>|
| group 2 (abatacept)<br> | Drug: Abatacept<br>* 10 mg/kg i.v. every 2 weeks twice, then every 4 weeks for 12 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dynamics of severity clinical and radiological symptoms | Dynamics of severity clinical and radiological symptoms of ILLD using scale score. | before the time the first dose of study treatment was administered | 
| Dynamics of severity clinical and radiological symptoms | Dynamics of severity clinical and radiological symptoms of ILLD using scale score. | 3 months of treatment | 
| Dynamics of severity clinical and radiological symptoms | Dynamics of severity clinical and radiological symptoms of ILLD using scale score. | 6 months of treatment | 
| Dynamics of severity clinical and radiological symptoms | Dynamics of severity clinical and radiological symptoms of ILLD using scale score. | 1 year of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of adverse events |  | from the time the first dose of study treatment was administered until 12 mo of treatment | 
| quality of life of patients | The quality of life of patients before and after therapy | before the time the first dose of study treatment was administered until 12 mo of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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interstitial lymphocytic lung disease, primary immunodeficiency, children, treatment, rituximab, abatacept