Comparative Effectiveness of Upadacitinib and Tofacitinib in Ulcerative Colitis: A US Propensity-Matched Cohort Study.
There are limited real-world data comparing the effectiveness of upadacitinib and tofacitinib in patients with ulcerative colitis (UC).
We conducted a retrospective cohort study using TriNetX, a multi-institutional database, to compare the effectiveness of upadacitinib and tofacitinib in patients with UC. The primary aim was to assess the risk of a composite outcome of hospitalization requiring intravenous steroids and/or colectomy within 6 and 12 months. One-to-one propensity score matching was performed for demographics, comorbid conditions, mean hemoglobin, C-reactive protein, albumin, and calprotectin, and prior UC medications including recent oral or intravenous steroid use between the cohorts. Risk was expressed as adjusted odds ratio (aOR) with 95% confidence intervals (CI).
There were 526 patients in the upadacitinib cohort (mean age 40.4 ± 16.3, 44.8% female sex, 76.6% White race) and 1,149 patients in the tofacitinib cohort (mean age 42 ± 17.1, 41.9% female sex, 76% White race). After propensity score matching, there was no significant difference in the risk of the composite outcome of need for intravenous steroids and/or colectomy within 6 months (aOR 0.75, 95% CI 0.49-1.09). However, there was a lower risk of the composite outcome (aOR 0.63, 95% CI 0.44-0.89) in the upadacitinib cohort compared with the tofacitinib cohort within 12 months. There was no difference in the risk of intravenous steroid use (aOR 0.70, 95% CI 0.48-1.02) but lower risk of colectomy (aOR 0.46, 95% CI 0.27-0.79). In sensitivity analysis, there was also a lower risk of the composite outcome (aOR 0.64, 95% CI 0.44-0.94), including lower risk of intravenous steroid use (aOR 0.67, 95% CI 0.45-0.99) and colectomy (aOR 0.49, 95% CI 0.26-0.92) in the upadacitinib cohort compared with the tofacitinib cohort within 12 months.
This study utilizing real-world data showed that upadacitinib was associated with improved disease-specific outcomes at 12 months compared with tofacitinib in patients with UC.
Kochhar GS
，Khataniar H
，Jairath V
，Farraye FA
，Desai A
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Raising the bar in ulcerative colitis management.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by growing incidence and prevalence around the world in the last few decades. The range of available existing treatment and strategies for its management is being implemented. Given the introduction of newly developed molecules and the lack of specific guidelines, drug positioning may represent a tough clinical challenge. UC management is mostly medical, and it has been shifting toward a more personalized approach with the aim to create a tailored strategy depending on the patient's profile. A treat-to target strategy seems to be the best approach to reach disease control as it allows to carry out therapeutic choices based on objective and specific parameters: histological, ultrasonographic, and molecular targets may add to the already used clinical, endoscopic, and biochemical targets. In addition, dual-targeted therapy has emerged as an attractive therapeutic strategy for patients not achieving remission. This review aims to provide an overview of the available strategies to raise the bar in UC.
Fanizzi F
，Allocca M
，Fiorino G
，Zilli A
，Furfaro F
，Parigi TL
，Peyrin-Biroulet L
，Danese S
，D'Amico F
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Sishen pills inhibit inflammatory dendritic cell differentiation via miR-505-3p mediated E-cadherin downregulation in ulcerative colitis.
Ulcerative colitis (UC) is an autoimmune disease that is highly susceptible to recurrence, which is still a lack of effective drugs with minor side effects in clinic. Intervention of inflammatory differentiation of dendritic cells (DCs) might be an effective strategy to treat UC. Sishen Pills (SSP) is a classic Chinese herbal formula which has been demonstrated the protective effect of UC, but the mechanism remains unclear.
To elucidate the protective effects of SSP against UC in mice and reveal its regulatory mechanism of DCs and the key active ingredients for the UC treatment based on transcriptomics, network pharmacology and experiments validation in vivo and vitro.
The key active ingredients of SSP were detected and screened integrating LC-MS/MS and network pharmacology. A mouse UC model was induced with 3% sodium dextran sulfate and treated with SSP for 14 days to evaluate the efficacy. ELISA was used to detect the levels of IL-6, IL-1β and TNF-α in the colon; flow cytometry was used to detect the expression levels of DCs and their subpopulations; whole transcriptomic sequencing of differential RNAs in the colon and RT-PCR to detect key miRNAs to verify the sequencing results. Mouse bone marrow-derived dendritic cells (BMDCs) were isolated, an inflammatory model was constructed using 100 ng/ml LPS, and the effects of SSP on DC proliferation and apoptosis and their surface co-stimulatory molecule expression were examined; IL-6, IL-1β, TNF-α levels were measured by ELISA; RT-PCR and WB were performed to detect miR-505-3p, CDH1, E-cadherin expression. BMDCs with low expression of miR-505-3p were constructed by lentiviral transfection for further validation. The potential key ingredient was re-validated in vivo and vitro experiment.
Animal experiments showed that SSP alleviated DSS-induced UC symptoms and colonic pathological injury in mice, and inhibited IL-6, IL-1β, TNF-α secretion and inflammatory DC proliferation and activation maturation. Network pharmacology predicted that evodiamine, isobavachalcone, curcumin, and engenol may play a key role in SSP. RNA sequencing revealed that miR-505-3p, as the differential miRNA, shared a large number of transcription factors with E-cadherin, and was involved in inflammatory differentiation regulation. In vivo experiments confirmed that SSP accelerated apoptosis, slowed down proliferation, inhibited inflammatory differentiation and IL-6, IL-1β, and TNF-α secretion in BMDCs, and decreased miR-505-3p, CDH1, and E-cadherin levels. After knocking down miR-505-3p, SSP could not regulate the inflammatory differentiation and IL-6, IL-1β, TNF-α level in BMDCs. Additionally, evodiamine was found and verified to be the key active ingredient of SSP in preventing the inflammatory differatiation of DCs.
SSP prevented the inflammatory differentiation of DCs by downregulating the expression of miR-505-3p, in which Evodiamine may played a key role.
Huang J
，Zhong Y
，Cheng N
，Zhang Z
，Huang L
，Song L
，Cheng S
，Zhao H
，Liu D
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