Background/Purpose: Interstitial lung disease (ILD) is a serious pulmonary manifestation that can occur across all connective tissue disorders (CTD). Aberrant immune-mediated inflammation and fibrosis leads to symptoms like dyspnea, cough, and respiratory failure, making ILD a major contributor to CTD morbidity and mortality. To better understand unmet therapeutic needs, characterization of real-world patient burden and treatment patterns is required. While epidemiologic studies have typically focused on single CTD populations, this study describes patient characteristics, comorbidities, and treatment utilization across a broad range of CTD-ILDs using a large electronic health record (EHR) database.

Methods: This retrospective cohort study (GSK Study 219992) used an Optum® de-identified EHR dataset of an incident cohort of patients with CTD-ILD diagnosed from 2018–2023. Published definitions and algorithms were used to identify CTD subtypes (RA, SSc, SLE, idiopathic inflammatory myopathies [IIM], MCTD, SS). Diagnoses of ILD after or within 365 days prior to CTD diagnosis were identified, with index being the first valid ILD diagnosis date within the study period. Baseline was 1 year prior to index. Patient follow-up was until death, discontinuation, or end of study period (Dec 31, 2023). Outcomes included baseline comorbidities and clinical characteristics, and treatment use.

Results: Baseline characteristics of eligible US patients with CTD-ILD by CTD subtype are shown in Table 1. ILD was diagnosed within ±1 year of CTD diagnosis in most patients (54–83%). Patients with RA and SLE were most likely to receive an ILD diagnosis >1 year after CTD (46% and 41%, respectively). Overlap with other CTD subtypes occurred in 11–38% of patients. The most frequently reported ILD symptom during the baseline period was dyspnea across all CTD subtypes (56–66%). Around 25% of patients in each CTD subtype had ≥3 comorbidities (Table 2). There was a high burden from infections requiring hospitalization (29–45% by CTD subtype), of which ~60% were due to acute respiratory infection. At baseline, 31–55% of patients were not receiving any oral/IV glucocorticoids (GC), immunosuppressants (IS), or advanced therapies across CTD subtypes. GC and IS were the most common treatments across all CTD-ILDs at any time (Figure). There was an increase in therapy following ILD diagnosis, with the proportion of patients receiving any treatment increasing from 45–70% at baseline to 74–88% in the first year. Even at the peak of treatment use in the first year, 12–26% of patients did not receive any oral/IV GC, IS, or advanced therapies. A trend of decreasing proportions of patients receiving any treatment was observed after the first year.

Conclusion: Patients with CTD-ILD suffer considerable chronic comorbidities that often have overlap with other CTDs, leading to high disease burden on healthcare systems and complex clinical management. Symptom burden and infections requiring hospitalization were high, highlighting a need for earlier diagnosis and treatment initiation. The observation that treatment use tended to decrease after the first year suggests an unmet need for optimal therapeutic management remains.

Table 1. Patient and clinical characteristics at baseline.

IQR, interquartile range.

Table 2. Selected comorbidities at ILD diagnosis.

CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; GERD, gastroesophageal reflux disease; MI, myocardial infarction.

Figure. Treatment use by CTD-ILD type at baseline and 12 months.

IS comprised cyclophosphamide, mycophenolate, azathioprine, methotrexate, calcineurin inhibitors, leflunomide; TNFi comprised etanercept, adalimumab, infliximab, golimumab, certolizumab pegol; anti-IL-6 comprised tocilizumab, sarilumab; anti-fibrotic agents comprised pirfenidone, nintedanib; JAK inhibitors comprised tofacitinib, baricitinib, upadacitinib.

IVIG, intravenous immunoglobulin; JAK, Janus kinase; TNFi, tumor necrosis factor inhibitor.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-high-disease-burden-of-connective-tissue-disorder-interstitial-lung-disease-in-the-usa-demonstrates-an-unmet-need-for-earlier-diagnosis-and-treatment/