LAUSR

Rituximab (RTX) is a new option in the treatment of systemic sclerosis (SSc) [1]. There is not enough data on changes in the level of autoantibodies and their clinical significance during RTM therapy. There are only a few reports on the higher efficiency of RTX in patients (pts) with SSc positive for anti-topoisomerase-1 antibodies (a-Topo-1), therefore the study of this issue might be interested.To compare clinical parameters and B-lymphocytes (B-lymph) level in SSc pts depending on the presence or absence of a-Topo-1 during RTX therapy with prospective long-term follow-up.This study included 88 pts with SSc. The mean follow-up period was 26,3±10,7 months. The mean age was 47years (17-71), female-73 pts (83%), the diffuse cutaneous subset of the disease had 50 pts (57%). Symptoms of the interstitial lung disease (ILD) were observed in 70 pts (80%). The mean disease duration was 5,9±4,8 years. The cumulative mean dose of RTX was 2,9±1,1 grams. All patients received prednisone at a dose of 11,7±4,4 mg, immunosuppressants received 42% of them. There were 63 pts positive for a-Topo-1 and 25 pts - negative. The pts of the compared groups did not differ in the main demographic and clinical parameters, excepting lung involvement. In a-Topo-1 positive group 55 (87%) pts had ILD and only 15 (60%) – in a-Topo-1-negative group (p=0,02). The results at baseline and at the end of the follow up are presented in the form of mean values and changes in parameters (delta).Considering the entire cohort, an improvement of almost all outcome parameters was found. When a-Topo-1 positive and a-Topo-1-negative pts were analyzed separately, we observed a significantly higher decrease in the activity score, depletion of B-lymph, an increase in forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) in a-Topo-1 positive group of pts (table 1).Table 1.Changes of the main outcome parameters depending on the presence of a-Topo-1 on RTX therapy.Parametersa-Topo-1positive ptsa-Topo-1negative ptsPDelta Activity score (EScSG-AI)1,790,90,001Delta Rodnan skin score (mRSS)4,95,2NSDelta B-lymphocytes (absolute count)0,2120,1930,001Delta FVC*, %8,646,460,001Delta DLCO**, %2,860,0320,001*FVC - forced vital capacity % predicted, **DLCO - diffusion capacity for carbon monoxide % predictedThe a-Тopo-1 level decreased from 174,2±50,1 to 148,1±66,1 units/ml (p=0,0009). In this group, a-Тopo-1 became negative in 5 pts (7,9%). The disappearance of a-Topo-1 positivity was accompanied by a more pronounced decrease in mRSS (delta mRSS=7,4) and a higher depletion of B-lymph. There was a higher cumulative dose of RTX (4±1,4grams) in this 5 pts compared with the pts who sustained a-Topo-1 positivity. There was a moderate negative statistically significant correlation between the a-Topo-1 and the total 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).In our study, the a-Topo-1 level significantly decreased during RTX therapy in Russian pts. The decrease in a-Topo-1 titers correlated with the total dose of RTX and was accompanied by a decrease in mRSS, disease activity index and an increase in FVC and DLCO. A higher efficacy of RTX in the a-Topo-1 positive group with prevalence of ILD was revealed, therefore a-Topo-1 positivity could be considered as a predictor of a better response to RTX therapy.[1]Jordan S, et al. Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group. Ann Rheum Dis.2015;74:1188–94.Doi:10.1136/annrheumdis-2013-204522.[2]Ebata S, Yoshizaki A, et.al. Rituximab therapy is more effective than cyclophosphamide therapy for Japanese patients with anti-topoisomerase I-positive systemic sclerosis-associated interstitial lung disease. J Dermatol.2019.Nov;46(11):1006-1013.doi:10.1111/1346-8138.15079.None declared