Developing a Screening Tool for Interstitial Lung Disease in People With Rheumatoid Arthritis Using Risk Factors

Study Overview
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Brief Summary
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The overall aim of the study is to develop and validate a Rheumatoid Arthritis-Interstitial Lung Disease (RA-ILD) clinical prediction model (screening tool) based on risk factors to guide screening for ILD in patients with RA using High Resolution Computed Tomography (HRCT).

Official Title
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A Prospective, Multi-national, Cross-sectional Study on a Risk-factor Guided Approach to Interstitial Lung Disease Screening in Patients With Rheumatoid Arthritis at Higher Risk for ILD Using High Resolution Computed Tomography

Conditions
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Arthritis, Rheumatoid, Lung Diseases, Interstitial

Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Adult patients with RA according to 1987 American College of Rheumatology (ACR) or 2010 ACR / European League Against Rheumatism (EULAR) classification of RA, with any RA duration Patient must have ≥ 2 of the following risk factors for ILD (i.e., any 2 or more): Male Current or previous smoker Age of ≥ 60 years at RA diagnosis Rheumatoid factor high-positive (titer > 3x upper limit of normal) AND/OR anti-cyclic citrullinated peptide (anti-CCP) high-positive (titer > 3x upper limit of normal) at RA diagnosis or any time after RA diagnosis High/severe RA disease activity score at screening visit or within 12 months of screening visit, as defined with any of the following measures: Disease Activity Score-28 (DAS-28), Clinical Disease Activity Index (CDAI), Routine Assessment of Patient Index Data 3 (RAPID-3), Simple Disease Activity Index (SDAI), Patient Activity Scale (PAS), PAS-II Presence or history of these extra-articular manifestations of RA: vasculitis, Felty's syndrome, secondary Sjogren's syndrome, cutaneous rheumatoid nodules, serositis and/or scleritis/uveitis Exclusion criteria: Patients previously diagnosed with any ILD or interstitial lung abnormality (ILA) Patients who have had a chest computerized tomography (CT) in the past 2 years Pregnancy at time of HRCT (to be checked in women of child-bearing potential before scan) Unwilling or unable to obtain HRCT Patients previously received drugs or treatments that are known to induce ILD (e.g., radiation therapy to chest region, bleomycin). Note: All disease-modifying antirheumatic drugs (DMARDs) including methotrexate and biologics are allowed. Patients who have had a lung transplant Patients suspected of having developed ILD due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection / coronavirus disease 19 (COVID-19) (based on Investigators' judgement) Patients diagnosed with another autoimmune disorders overlapping with RA-associated with the development of ILD (systemic sclerosis, myositis, dermatomyositis, mixed connective tissue disease, systemic lupus erythematosus, antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis or primary Sjogren's syndrome) Patients currently enrolled in an investigational new drug trial

Ages Eligible for Study
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Minimum 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 |
| --- | --- |
| Patients with Rheumatoid Arthritis (RA)<br>RA and 2 or more risk factors for developing Interstitial Lung Disease (ILD) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Probability score based on multi-variable diagnostic model that incorporates risk factors commonly available in clinical practice for RA-ILD screening | The endpoint of the model will be to recommend screening HRCT scan based on risk factors. | up to 1 year | 
| Prevalence of RA-ILD and radiological features of RA-ILD on HRCT |  | up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demographics of patients with and without ILD symptoms | Age, sex, race (Baseline characteristics) | up to 1 year | 
| Disease characteristics of patients with and without ILD symptoms: Duration of Rheumatoid Arthritis |  | up to 1 year | 
| Disease characteristics of patients with and without ILD symptoms: Disease Activity Score (DAS) 28 | The DAS28 score ranges from 0 to 9.4 with higher values reflecting a higher disease activity. | up to 1 year | 
| Disease characteristics of patients with and without ILD symptoms: Forced Vital Capacity |  | up to 1 year | 
| Disease characteristics of patients with and without ILD symptoms: Diffusing Capacity for Carbon Monoxide |  | up to 1 year | 
| Diagnostic performance of clinical prediction model in asymptomatic and symptomatic sub-populations | The overall apparent performance of the model will primarily be assessed using the Brier Score. Discrimination will be assessed using the Area Under the Curve (AUC) (c-statistic) and callibration will be analysed with a calibration plot. | up to 1 year | 
| Correlation of abnormal findings on pulmonary function testing (PFT) and auscultation relevant to ILD to HRCT findings |  | up to 1 year |