Most RA-ILD biomarker studies enroll patients receiving treatment, which may alter inflammatory activity. We investigated whether calprotectin, sialic acid, and pannexin-1 show treatment-adjusted cross-sectional associations with ILD status in patients receiving treatment for RA. This cross-sectional case-control study included 154 participants (49 patients with HRCT-confirmed RA-ILD, 55 RA patients without ILD, 50 healthy controls). Serum biomarkers were measured by ELISA. The primary multivariate logistic regression model for ILD status within the RA cohort was adjusted for age, sex, smoking status, and binary biologic DMARD and corticosteroid use, with VIF, L1/L2 penalized, parsimonious model, rituximab-exclusion resampling, and bootstrap-CI ROC sensitivity analyses. In Bonferroni-corrected pairwise testing between RA-ILD and RA without ILD, no biomarker reached p<0.017 (ESR p=0.97, CRP p=0.72, calprotectin p=0.092, sialic acid p=0.90, pannexin-1 p=0.066). After adjustment, three biomarkers showed independent associations with ILD: lower calprotectin (OR=0.21, 95% CI 0.08–0.57, p=0.002, q=0.006), higher age-adjusted sialic acid (OR=2.57, 1.22–5.45, p=0.013, q=0.020), and lower pannexin-1 (OR=0.52, 0.28–0.94, p=0.029, q=0.029). All VIFs were below 1.25; Ridge and Lasso regression retained the same three biomarkers. AUCs were modest, with all five 95% CIs including 0.50 (pannexin-1 0.61; calprotectin 0.60). These findings indicate that serum calprotectin, sialic acid, and pannexin-1 carry weak conditional associations with ILD status in patients receiving RA treatment. However, their discriminatory performance is insufficient for standalone clinical use.