Latest! What is the progress of the stratification and treatment of dry syndrome? EULAR 2020.

EULAR 2020, let's listen! Editor's note: on June 3, 2020, the European annual meeting on rheumatism (EULAR) officially opened.due to the impact of the covid-19 epidemic, this meeting was held online.in order to grasp the latest and hottest international cutting-edge trends in the field of Rheumatology and immunology, "rheumatism and nephropathy channel of medical circles" specially invited Zhang Xia, chief physician of Department of Rheumatology and immunology, people's Hospital of Peking University, to present a wonderful report of the meeting! Sjogren's syndrome has complex etiology, diverse clinical manifestations, high risk of lymphoma. The corresponding relationship between abnormal immune regulation and clinical symptoms is not clear, such as fatigue, pain and other clinical manifestations of target tissue is not clear.due to the diversity of SS diseases, it is challenging to define a reliable endpoint in clinical monitoring and clinical trials.in order to find a hierarchical method based on clinical symptoms and explore the relationship between clinical symptoms and disease pathology and treatment response, Wan Fai from Newcastle University, UK, was invited Professor ng conducted a meta-analysis of five common clinical symptoms (pain, fatigue, dryness, anxiety, and depression) of xerosis, and used the UK SS Registry (ukpssr) for regression analysis. Four groups were defined: low symptom burden (LSB), high symptom burden (HSB), and dryness dominion with fatigue (DDF), Pain dominant with fatigue (PDF).the concentration of anti SSA, anti SSB antibody, IgG, β 2 microglobulin, CXCL13 concentration and transcriptomics model in peripheral blood were statistically different among the groups. The same results were obtained by using SS registration databases in Norway and France.based on the stratified results, the reanalysis of the two clinical trials showed that there was a significant difference in the treatment of hydroxychloroquine in the HSB group compared with the control group, while there was a significant difference in the treatment of rituximab in the DDF group compared with the placebo group.therefore, patient stratification provides more reliable evaluation indicators for clinical disease monitoring, treatment decision-making and clinical trial design.Xavier, University of Paris, France Professor mariette explained in detail the new progress in the treatment of Sjogren's syndrome. Based on the pathogenesis of SS, the clinical research progress related to treatment is as follows: acting on T cells and cytokines: (1) the study found that serum IL-17 and interferon in SS patients were increased, which promoted the interaction between glandular epithelial cells and T cells, and anti-il-17r monoclonal antibody (ose-127) could reduce SS patients' stem cells In addition, the interaction between T cells and epithelial cells was inhibited.(2) a prospective clinical study of leflunomide combined with hydroxychloroquine in the treatment of SS showed that the levels of essdai and esspri were significantly lower than those at baseline, and IgG levels were decreased, suggesting that leflunomide may inhibit the activation of B cells at the same time.(3) with regard to the treatment of SS with abacept acting on T cells, the latest two clinical studies found that there was no significant difference between the abacept treatment group and the placebo control group at 169 days.effects on B cells and BAFF: (1) a randomized phase IIa clinical study of anti-CD40 monoclonal antibody (cfz533) in the treatment of SS, including 29 patients in the cfz533 group (including 8 cases of subcutaneous 3 mg / kg or 21 cases of 10 mg / kg static point) and 15 cases of placebo control group. The results showed that compared with the control group at 12 weeks, the essdai of cfz533 (10mg / kg) group decreased by 5.64, the efficacy of 3mg / kg group was not obvious, and the safety was not significant except one case of atrial fibrillation Other adverse reactions.(2) previous studies found that the increase of serum BAFF level after rituximab treatment will increase the activation of self reactive B cells. Therefore, it may be beneficial to inhibit the activation of self reactive B cells by anti BAFF therapy after rituximab treatment.Kevin Chevalier and others used anti BAFF monoclonal antibody to treat 3 patients with refractory Ss who did not respond well to conventional medication and rituximab treatment. The results showed that after 3 months of treatment, the essdai of the patients decreased significantly compared with the baseline, the hormone gradually decreased, and the patient's condition improved.(3) at present, anti BAFF receptor monoclonal antibodies with both B-cell clearance and BAFF inhibition functions are in clinical trials.at the meeting, Professor Thomas D ü rner from Berlin, Germany, introduced in detail the 52 week phase 2B randomized double-blind placebo clinical study of anti BAFF receptor monoclonal antibody ianalumab (vay736) in the treatment of Sjogren's syndrome, mainly defining the dosage, clinical efficacy and safety.190 dry patients with ESS Dai ≥ 6 and esspri ≥ 5 were randomly divided into four groups at 1:1:1:1. Vay736, 5mg, 50mg, 300mg and placebo were given subcutaneously. The change of essdai from baseline at 24 weeks was the main end point.the study found that at 24 weeks, the response rate of essdai in the 300mg dose group (89.4%) was 28.1% higher than that in the placebo control group (61.2%), but there was no significant difference between the 5mg and 50mg dose groups and the control group, and there was no significant adverse reaction in each group.acts on plasma mother cells and plasma cells, such as anti-CD38 monoclonal antibody (daratumab), anti BCMA monoclonal antibody, etc., but at present, these new drugs are mainly used in multiple myeloma research and application, in the field of autoimmunity in the future need further research.Others: at present, a variety of new drugs for the treatment of xerosis with different targets are being studied in clinical trials (see Figure), others such as PI3 kinase inhibitors, JAK inhibitors, etc.to sum up, due to the complexity and diversity of SS diseases, it is a challenge to find reliable indicators to evaluate the efficacy of clinical trials. Patients with different phenotypes or different levels of SS have different response to treatment drugs. At present, an international multicenter trial (necessity) based on hierarchical management of patients to explore new clinical endpoint indicators is under way and needs further study in the future One step study.