Predictors of rituximab efficacy in systemic sclerosis-associated interstitial lung disease: machine-learning analysis of the DESIRES trial

Abstract Objectives Rituximab is emerging as a promising therapeutic option for systemic sclerosis-associated interstitial lung disease (SSc-ILD). However, little is known about factors that predict the efficacy of rituximab in SSc-ILD. Methods A post-hoc analysis was performed on prospective data from 48 patients with SSc-ILD in the double-blind, randomized, placebo-controlled DESIRES trial. A total of 28 baseline factors were selected as candidates to predict the efficacy of rituximab on the percentage of predicted forced vital capacity (ppFVC) at 24 weeks. A machine learning causal tree algorithm was used to explore the combination of predictors to identify subpopulations with a good response to rituximab. Results Serum levels of C-reactive protein (CRP) and Krebs von den Lungen-6 (KL-6) were selected as branches of the decision tree to stratify patients into 3 subpopulations. In the subpopulation with serum CRP levels ≥ 0.055 mg/dl, ΔppFVC was significantly higher in the rituximab group than in the placebo group (difference 8.01% [95% CI: 4.40%, 11.62%]). In the subpopulation with serum CRP levels < 0.055 mg/dl and serum KL-6 levels ≥ 364 U/ml, ΔppFVC was comparable between the two groups (difference 2.47% [95% CI: -1.99%, 6.92%]). In the subpopulation with serum CRP levels < 0.055 mg/dl and serum KL-6 levels < 364 U/ml, ΔppFVC was significantly lower in rituximab than in placebo (difference -6.85% [95% CI: -10.80%, -2.91%]). Conclusion Even slight elevations in serum CRP levels are associated with the improvement in ppFVC and may serve as predictors of rituximab efficacy in SSc-ILD.