Clinical and Therapeutic Challenges in Connective Tissue Disease and ILD Save

Connective tissue diseases (CTDs) and interstitial lung disease (ILD) represent a challenging intersection of systemic autoimmunity and progressive respiratory impairment. Research presented at EULAR 2025 continues to highlight the importance of CTD-ILD and the evolving landscape of therapeutic options for patients with autoimmune ILDs.

A national epidemiological study from France presents comprehensive population-level data on CTD-ILD across six major autoimmune diseases: rheumatoid arthritis (RA), primary Sjögren syndrome, mixed connective tissue disease (MCTD), systemic lupus erythematosus, idiopathic inflammatory myopathies and systemic sclerosis (abstract OP0033). Looking at data from over 228,000 incident CTD cases using the French national health insurance database, the authors highlight the significant burden of ILD, particularly progressive pulmonary fibrosis (PPF), across all CTDs.

While the prevalence of ILD varied widely by disease subtype, from 2% in RA to 36.8% in myositis, it consistently conferred a markedly increased risk of mortality. Importantly, PPF, a phenotype associated with rapid disease progression and poor outcomes, was seen in a significant proportion of those with ILD, ranging from 2.6% in SLE to 34.1% in RA. For numerous patients, ILD was diagnosed months before or after the CTD itself, highlighting a diagnostic window in which earlier recognition and intervention may be possible.

These findings underscore the urgency of systematic ILD screening in CTD populations, particularly given the mortality signal observed. But they also reinforce the need for effective, tolerable treatments once ILD, especially PPF, is established.

To that end, a therapeutic highlight at EULAR 2025, due to be presented in the late-breaking abstract session (abstract LB0003), is the subgroup analysis of autoimmune ILD patients within the large Phase III FIBRONEER-ILD trial. The trial evaluated nerandomilast, a selective phosphodiesterase 4B inhibitor with immunomodulatory and antifibrotic effects. Among the 325 patients with autoimmune ILD, including those with RA, systemic sclerosis and MCTD, nerandomilast significantly slowed the decline in forced vital capacity compared to placebo. A dose of 18 mg twice daily was associated with a statistically significant reduction in time to first acute exacerbation, respiratory hospitalisation or death (HR 0.56 [95% CI: 0.33, 0.96]). The safety profile of nerandomilast was acceptable, with no increase in serious adverse events or treatment discontinuation compared to placebo.

Taken together, these studies illustrate the scale of both the clinical and therapeutic challenges in CTD-ILD. The population-based French data highlight the need for earlier and broader detection strategies, while FIBRONEER-ILD suggests a potential new oral treatment option for patients with CTD-ILD.

CTD-ILD is a critical driver of morbidity and mortality in systemic autoimmune conditions. These data will be central to shaping screening policies, therapeutic decision-making, and future research agendas.