Advances and future outlook in clinical trials for treating systemic sclerosis-interstitial lung disease

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is a common complication of systemic sclerosis (SSc), contributing significantly to morbidity and mortality. We aim to bridge knowledge gaps, inform clinical practice, and identify future research directions in this rapidly evolving field.

This review provides a comprehensive analysis of the current understanding and emerging advances in the diagnosis, risk stratification, and treatment of SSc-ILD. High-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) remain cornerstones of diagnosis, but limitations in sensitivity underscore the need for biomarkers such as Chemokine (C-C motif) Ligand 18 (CCL18), Krebs von den Lungen-6 (KL-6), Interleukin-6 (IL-6), and C-reactive protein (CRP) to enhance prognostic precision and treatment personalization. Therapeutic strategies emphasize immunosuppressants alongside antifibrotic agents. Emerging combination therapies and advanced modalities, including hematopoietic stem cell transplantation and chimeric antigen receptor T-cell therapy, show promise in refractory cases. Ongoing clinical trials exploring innovative targets highlight the evolving therapeutic landscape. The review emphasizes challenges in clinical trial design, advocating for adaptive and platform trial methodologies to address disease heterogeneity and enhance treatment sensitivity.

Advances in biomarkers, composite indices, and personalized therapeutic approaches are key to overcoming existing limitations and improving outcomes for patients with SSc-ILD.