DECREASE OF ANTI-TOPOISOMERASE-1 ANTIBODY IN PATIENTS WITH INTERSTITIAL LUNG DISEASE, ASSOCIATED WITH SYSTEMIC SCLEROSIS, AS A PREDICTOR OF BETTER RESPONSE ON RITUXIMAB THERAPY

Abstract

TOPIC: Diffuse Lung Disease TYPE: Original Investigations PURPOSE: To compare clinical parameters and B-lymphocytes (B-lymph) level in systemic sclerosis (SSc) patients depending on the decrease of anti-topoisomerase-1 antibody (a-Topo-1) during rituximab (RTX) therapy with prospective long-term follow-up. METHODS: This study included 63 patients with SSc. The mean follow-up period was 26,3±10,7 months. The mean age was 47 years (18-66), female-53 patients (84%), the diffuse cutaneous subset of the disease had 39 patients (62%). Symptoms of the interstitial lung disease (ILD) were observed in 60 patients (95%). The mean disease duration was 6,03±4,9 years. The cumulative mean dose of RTX was 2,9±1,1 grams. All patients received prednisolone at a dose of 11,1±4,4 mg, immunosuppressants at inclusion received 43% of them. All patients were positive for a-Topo-1. Patients were divided into 2 groups depending on the changes of a-Topo-1 on RTX therapy: group 1 (n=32) – patients with decrease in a-Topo-1 and group 2 (n=31) – patients with stable level of a-Topo-1. Patients of the compared groups did not differ in the main demographic and clinical parameters, except disease subset: there was 47% of patients with diffuse cutaneous subset in group 1 and 80% of them in group 2. The results are presented in the form of mean values and changes in parameters (delta(Δ) - difference between the baseline parameter and follow up point). RESULTS: Considering the entire cohort, an improvement of almost all outcome parameters was found. In group 1 there was ΔActivity score (EScSG-AI)=1,93; ΔRodnan skin score (mRSS)=5,33; ΔB-lymph (absolute count)=0,222; Δforced vital capacity % predicted (FVC)=11,9; Δdiffusion capacity for carbon monoxide % predicted (DLCO)=3,2; cumulative mean dose of RTX=3,3±1,2 mg. In group 2 there was ΔActivity score (EScSG-AI)=1,84; ΔmRSS=4,68; ΔB-lymph=0,223; ΔFVC=5,75; ΔDLCO=2,73; cumulative mean dose of RTX=2,7±0,9 mg. When groups were analyzed separately, we observed a significantly higher increase of FVC (p=0,03) and DLCO (p=0,02) in group 1. In group 1 the a-Тopo-1 level decreased from 174,2±50,1 to 148,1±66,1 units/ml (p=0,0009). There was a moderate negative statistically significant correlation between the a-Topo-1 and cumulative mean dose of RTX (r=-0,298, p=0,017). A moderate negative statistically significant correlation was found between the a-Topo-1 and FVC (r=-0,322, p=0,009). CONCLUSIONS: In our study, the a-Topo-1 level significantly decreased during RTX therapy. The decrease of a-Topo-1 level correlated with the cumulative mean dose of RTX and an increase of FVC, and was accompanied by a decrease of mRSS, disease activity index and an increase of DLCO. There was a greater increase of FVC and DLCO in the group of patients with a decrease of a-Topo-1. CLINICAL IMPLICATIONS: Therefore, decrease of a-Topo-1 could be considered as a predictor of a better response on RTX therapy in patients with ILD associated with SSc. DISCLOSURES: No relevant relationships by Lidia Ananyeva, source=Web Response No relevant relationships by Oxana Desinova, source=Web Response No relevant relationships by Liudmila Garzanova, source=Web Response No relevant relationships by Olga Koneva, source=Web Response No relevant relationships by Olga Ovsynnikova, source=Web Response No relevant relationships by Rushana Shayakhmetova, source=Web Response No relevant relationships by Mayya Starovoytova, source=Web Response