ABSTRACT
Crohn’s Disease （CD） is a destructive， relapsing and remitting chronic inflammatory bowel disease that usually progresses to irreversible intestinal structural and functional changes， such as intestinal lumen stenosis， fistula formation and perianal lesions， severely affecting the quality of life of patients. This review summarized the research progress on the mechanism， clinical application and safety of upadacitinib in the treatment of CD. Upadacitinib can increase the clinical remission and endoscopic response rates in patients with CD， improve the long-term outcome of CD patients and provide a new idea for the treatment of CD patients by using biological agents.
ABSTRACT
Objective To investigate the effects of upadacitinib on the polarization and inflammation of BV2 microglia after oxygen glucose deprivation/recovery (OGD/R) and to explore its mechanism of action. Methods The experiment was divided into 3 groups: control group, OGD group and upadacitinib treatment group. After BV2 cells were treated with OGD/R, MTT was used to detect cell survival rate. Wound scratch assay was used to detect the cell migration ability. qPCR was used to detect mRNA levels of M1-type polarization markers (CD11b, CD32, iNOS) and M2-type polarization markers (Arg-1, IL-10, CD206) of BV2 cells. ELISA was used to detect the levels of IL-1β, IL-6, and TNF-α in the culture medium. Western blot was used to detect the expression levels of JAK1/STAT6 pathway-related proteins. Results Upadacitinib increased the survival of BV2 cells after OGD/R (P<0.05), reduced the polarization of BV2 cells to M1 type (P<0.05). Upadacitinib significantly decreased the migration ability of BV2 cells induced by OGD/R (P<0.05), reduced the inflammatory factors secreted by BV2 cells induced by OGD/R: IL-1β, IL-6, TNF-α (P<0.05). Upadacitinib increased the survival rate of co-cultured PC12 cells (P<0.05). Upadacitinib significantly inhibited the expression levels of p-JAK1 and p-STAT6 proteins in BV2 cells activated by OGD/R induction (P<0.05). Conclusion Upadacitinib decreases polarization of BV2 induced by OGD/R to M1 type and reduces inflammation, which is related to JAK1/STAT6 pathway.
ABSTRACT
OBJECTIVE： To evaluate the therapeutic efficacy and safety of 2 kinds of selective Janus kinase 1 （JAK-1） inhibitor Upadacitinib and Filgotinibfor in the treatment of rheumatoid arthritis， and to provide evidence-based reference for clinical treatment. METHODS： Retrieved from PubMed， Medline， Embase， the Cochrane library， CBM， CJFD， Wanfang database and VIP， RCTs about placebo （control group） versus Upadacitinib or Filgotinibfor （trial group） in the treatment of rheumatoid arthritis on the basis of methotrexate or other antirheumatic drugs were collected during the establishment of the database to Jan. 2019. Meta-analysis of therapeutic efficacy [the proportion of patients with remission rate of 20％ （ACR20）， ACR50， ACR70 according to the criteria of American Rheumatism Association， the proportion of patients with 28-joint disease activity score （DAS28）＜3.2] and safety [the incidence of adverse event （AE）， severe adverse event （SAE）， infection， severe infection， herpes zoster， liver injury] were conducted by using Rev Man 5.3 software after data extraction and quality evaluation with Cochrane system evaluator manual 5.1.0. RESULTS： A total of 8 RCTs were included， involving 2 738 patients. Meta-analysis showed that the proportion of patients with ACR20 [OR＝3.37，95％CI（2.80，4.05），P＜0.001]， ACR50 [OR＝3.78，95％CI（2.98，4.78），P＜0.001] and ACR70 [OR＝4.31，95％CI（3.05，6.09），P＜0.001]， the proportion of patients with DAS28＜3.2 [OR＝3.86，95％CI（2.98，5.00），P＜0.001]， the incidence of AE [OR＝1.33，95％CI（1.11，1.61）， P＝0.002]， the incidence of infection [OR＝1.43，95％CI（1.12，1.81），P＝0.004] in trial group were significantly higher than control group； there was no statistical significance in other indexes （P＞0.05）. CONCLUSIONS： JAK-1 inhibitors Upadacitinib and Filgotinib can improve the effect indexes of ACR20， ACR50 and ACR70 and the proportion of patients with DAS28＜3.2 of rheumatoid arthritis patients； it can not increase the incidence of SAE， severe infection， herpes zoster， liver injury， but can increase the risk of AE and infection.