STUDY OF RITUXIMAB EFFICACY PREDICTORS IN PATIENTS WITH SYSTEMIC SCLEROSIS WITH INTERSTITIAL LUNG DISEASE

Abstract

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Original Investigations PURPOSE: The study of potential efficacy predictors of anti-B-cell therapy in the patients with SSc associated with ILD. METHODS: 90 patients with SSc-ILD verified by multispiral computed tomography were enrolled to the study and received RTM therapy for 12-42 months at cumulative dose 2.9±1.1 grams (disease duration 5.9±4.8 years, diffused/limited SSc 1.3/1, average age 47 ± 13.6 years, females 83%). All patients received low or moderate dose glucocorticoids. 45 patients received RTM in addition to immunosuppressive therapy (cyclophosphamide and mycophenolate mofetil) because of inadequate efficacy of immunosuppressants. After evaluation of FVC trends in the patients receiving RTM the overall study population was divided into two patient groups for the analysis: group A (n=35) comprised the patients with ≥10% FVC increase (disease duration 6.1±5.8 years, diffused/limited SSc 1,3/1, average age 50±12 years, females 86%, cumulative RTM dose 3.2±1.24 grams), and group B (n=11) comprised the patients with ≥5% FVC decrease (disease duration 5.2±4, diffused/limited SSc 0.8/1, average age 43±16, females 72%, cumulative RTM dose 2.5±0.99 grams). Subsequently correlation analysis was made to clarify the association between delta FVC and a number of clinical (age, gender, duration and form of SSc, modified skin count, presence of gastroesophageal reflux, mPAP, SSc activity (EScSG, points), cumulative RTM dose, immunosuppressive therapy) and laboratory parameters (ESR, ANA-НЕР-2, a-Scl-70, CRP, B cell count). RESULTS: In the overall patient population RTM therapy was associated with significant FVC increase from 77.0±19.9 % to 84.7±20.9% (р=0.000000), with median FVC increment 6.6% [0 ;14.1].In group A FVC increased from 75.3±19.9 to 94.3±20.4) (р=0.000000), with median FVC increment 16.3 [12.6; 24.7].In group B FVC decreased from 82.5 ±23.2 to 72,3±19.4 (р=0,000176), with median FVC decrement 10.4% [-13.4; -6].Correlation analysis in groups A and B showed significant association of between delta FVC and the patient age (R=0.36), cumulative RTM dose (R=0.34) and EScSG during the last examination (1.2±.,0 and 3.1±1.4 in groups A and B, respectively; R=-0.42).No significant correlation between delta FVC and any other tested parameters was found. CONCLUSIONS: Therefore, older patients who received the cumulative rituximab dose more than 3 grams with suppressed SSc activity achieved greater FVC increase at the background of therapy. These data allow to consider the above parameters as potential predictors of response to anti-B-cell therapy in the patients with SSc-ILD. CLINICAL IMPLICATIONS: The obtained data will increase the effecacy of anti-B-cell therapy in patients with SSc associated with ILD. 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 Mayya Starovoytova, source=Web Response