LAUSR

OBJECTIVES The DESIRES trial showed that rituximab is effective in treating skin sclerosis in systemic sclerosis. However, which patient groups are likely to benefit from rituximab is unknown. METHODS We performed post-hoc analysis on prospective data from 54 patients who received rituximab or placebo in the DESIRES trial. Twenty-seven baseline factors were used to investigate subpopulations with different magnitudes of rituximab effect on modified Rodnan Skin Score (mRSS) change at 24 weeks. Based on a machine-learning algorithm called the causal tree, we explored the combination of predictors needed to identify subpopulations that would respond to rituximab and have good treatment outcomes. RESULTS Three factors were identified as branches of the decision tree: "peripheral blood CD19-positive cell counts", "mRSS", and "serum surfactant protein D (SP-D) levels". Only in the subpopulation of patients with CD19-positive cell counts < 57/μl, rituximab did not show a significant improvement in mRSS vs placebo. In the subpopulation of patients with CD19-positive cell counts ≥ 57/μl and mRSS ≥ 17, mRSS was most improved with rituximab (difference -17.06 [95%CI -24.22 to -9.89]). The second greatest improvement in mRSS with rituximab was in the subpopulation with CD19-positive cell counts ≥ 57/μl, mRSS < 17, and serum SP-D levels ≥ 151 ng/ml (difference -10.35 [95% CI -14.77 to -5.93]). CONCLUSION Systemic sclerosis patients who have high CD19-positive cell counts and high mRSS expected greater improvement in mRSS with rituximab. When the patients with high CD19-positive cell counts showed low mRSS, serum SP-D levels may modify the treatment effect. TRIAL REGISTRATION ClinicalTrials.gov, https://clinicaltrials.gov, NCT04274257 and UMIN-CTR, https://center6.umin.ac.jp, UMIN000030139.