Pulmonary Function and Radiographic Outcomes in Systemic Sclerosis-Associated Interstitial Lung Disease: A Systematic Review of Rituximab, Interleukin-6 Inhibitors, and Janus Kinase Inhibitors.

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is a major cause of morbidity and mortality in systemic sclerosis patients. Although management typically includes conventional immunosuppression, increasing attention has been given to targeted immunomodulatory therapies including rituximab (RTX), IL-6 inhibitors (IL-6i), and JAK inhibitors (JAKi). This systematic review aimed to synthesize the available evidence on target immunomodulation as a management strategy for SSc-ILD, with a focus on post-exposure pulmonary function testing and radiographic progression. A systematic literature review was conducted utilizing EMBASE, Ovid MEDLINE, PubMed, and Web of Science in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The targeted population included adult patients with either SSc-ILD or extractable pulmonary outcomes. Outcomes of interest included forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO), total lung capacity (TLC), and high-resolution computed tomography (HRCT) progressive outcomes. Twenty-three studies met the inclusion criteria. FVC was the most consistently reported pulmonary outcome, while DLCO, TLC, and serial HRCT outcomes were less uniformly assessed. Due to substantial heterogeneity within the selected studies, a meta-analysis was not performed; findings were synthesized narratively. Targeted immunomodulatory therapy was more commonly associated with stabilization of pulmonary function rather than with substantial improvement. Tocilizumab demonstrated the strongest evidence for relative FVC preservation in placebo-controlled studies while RTX showed recurrent stabilization signals across comparative and observational studies. Evidence for JAKi remained premature, with limited pulmonary function data and inconsistent outcome reporting. Substantial heterogeneity in study design, patient populations, concomitant immunosuppression, comparators, and outcome reporting limited direct comparison across the therapies evaluated. Future research should account for inconsistencies amongst studies, namely population sizes, concurrent therapies, study types, and comparison groups. Future prospective studies using standardized criteria, outcome definitions, and comparator groups are needed to improve the causal interpretation.