# Defining the molecular and radiologic phenotype of progressive RA-ILD

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2023 · $652,982

## Abstract

Research Objective: The objective of our proposed research is to identify patients with rheumatoid arthritis
associated interstitial lung disease (RA-ILD) that are at the highest risk for progressive disease and may
potentially benefit from more targeted, and potentially less harmful, treatment. Unmet Health Need: Deaths
from RA-ILD are not improving despite an overall decline in RA mortality. Novel, noninvasive methods are
urgently needed to identify those with progressive RA-ILD so that interventions can delay the development of
end-stage lung disease. Rationale: RA-ILD is a heterogeneous condition and the majority will experience
disease progression resulting in lung transplantation and/or death. Despite the heterogeneity of RA-ILD, all
RA-ILD is treated the same without taking in to account the known heterogeneity of this disease. This
immunosuppressive-based treatment approach has led to unpredictable natural histories, inconsistent
responses to treatment, and ultimately irreversible fibrosis leading to increased symptom burden, worse quality
of life, and ultimately death. Hypothesis: Our overall hypothesis is that novel quantitative imaging and specific
blood markers will be associated with a progressive phenotype in RA-ILD. Aims: We will evaluate the role of
novel quantitative imaging (Specific Aim 1), peripheral blood telomere length (Specific Aim 2) and peripheral
blood mononuclear cell (PBMC) gene expression (Specific Aim 3) in predicting progressive RA-ILD as defined
by 12-month change in FVC% predicted. We will also explore the overlap and additive strength of each of
these predictors in a composite profile (Specific Aim 4). Approach: To achieve the proposed aims, we will
recruit 364 subjects with RA-ILD at the time of ILD diagnosis by an ILD pulmonologist and prior to treatment
with lung-specific immunosuppression. Recruitment will occur at 4 expert ILD centers across the country with
longitudinal collection of clinical, physiologic, and radiologic data with collection of serial biospecimens. The
overall goal of this proposal is to identify the subset of RA-ILD patients that are at highest risk for disease
progression following diagnosis by using novel imaging and specific blood markers. This risk stratification will
help us determine whether or not immunosuppression should be started on an RA-ILD patient at the time of
diagnosis. This knowledge will ultimately lead to less harm to patients with RA-ILD by decreasing exposure to
immunosuppression in the subset that is most vulnerable. This proposal will lead to future precision-medicine
based investigations for RA-ILD treatment and will lay the foundation to perform clinical trials that will
determine the role of additional treatment pathways (e.g., observation, antifibrotic therapy, novel therapeutics
and/or combination therapy) in RA-ILD, leading to reduction in harm and delaying the development of end-
stage lung disease.

## Key facts

- **NIH application ID:** 10634344
- **Project number:** 1R01HL168126-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Joyce Sujin Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $652,982
- **Award type:** 1
- **Project period:** 2023-08-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10634344

## Citation

> US National Institutes of Health, RePORTER application 10634344, Defining the molecular and radiologic phenotype of progressive RA-ILD (1R01HL168126-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10634344. Licensed CC0.

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