A Prospective Trial with Long Term Follow-up of Patients With Severe, Steroid-Resistant Ulcerative Colitis Who Received Induction Therapy With Cyclosporine and Were Maintained With Vedolizumab

Tarabar, Dino; Jurdi, Katia El; Yvellez, Olivia; Milenković, Zoran; Petrović, Stanko; Subotić, Bojana; Gils, Ann; Brocic, Tanja; Brcerevic, Irina; Latinovic, Olgica; Jocic, Tanja; Rubin, David T.

doi:10.1093/ibd/izab328

Cited by 12 publications

(7 citation statements)

References 19 publications

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“…Newer agents such as vedolizumab, ustekinumab, and ozanimod have been studied in ASUC but largely as maintenance therapy following a cyclosporine bridge [44,46,[71][72][73][74]. Unfortunately, interim futility analysis of a multicenter trial of interleukin-1 blockade with anakinra did not reduce the need for rescue therapy or colectomy compared with placebo [75,76].…”

Section: Ifxmentioning

confidence: 99%

In-hospital management of inflammatory bowel disease

Berinstein

Aintabi

Higgins

2023

Current Opinion in Gastroenterology

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Purpose of reviewThe management of hospitalized patients with inflammatory bowel disease (IBD) is complex. Despite considerable therapeutic advancements in outpatient ulcerative colitis and Crohn's disease management, the in-hospital management continues to lag with suboptimal outcomes. The purpose of this review is to provide a brief overview of our approach to managing patients hospitalized with acute severe ulcerative colitis (ASUC) and Crohn's disease-related complications, followed by a summary of emerging evidence for new management approaches.Recent findingsASUC has seen the emergence of well validated prognostic models for colectomy as well as the development of novel treatment strategies such as accelerated infliximab dosing, Janus kinase inhibitor therapy, and sequential therapy, yet the rate of colectomy for steroid-refractory ASUC has not meaningfully improved. Crohn's disease has seen the development of better diagnostic tools, early Crohn's disease-related complication stratification and identification, as well as better surgical techniques, yet the rates of hospitalization and development of Crohn's disease-related complications remain high.SummarySignificant progress has been made in the in-hospital IBD management; however, both the management of ASUC and hospitalized Crohn's disease remain a challenge with suboptimal outcomes. Critical knowledge gaps still exist, and dedicated studies in hospitalized patients with IBD are needed to address them.

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Section: Ifxmentioning

confidence: 99%

In-hospital management of inflammatory bowel disease

Berinstein

Aintabi

Higgins

2023

Current Opinion in Gastroenterology

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“…The colectomy rate after a median of 25 months of follow‐up was 42%. A recent prospective study also evaluated bridging ciclosporin with vedolizumab in 15 patients with steroid‐refractory ASUC 40 (Table 5). More recently, given the increasing exposure to anti‐TNF and vedolizumab, a small retrospective study of 10 patients evaluated the safety and efficacy of CNIs as a bridge to ustekinumab in ASUC 41 .…”

Section: Medical Management Of Acute Severe Ulcerative Colitismentioning

confidence: 99%

Review article: Updated management of acute severe ulcerative colitis: From steroids to novel medical strategies

Calméjane

Laharie

Kirchgesner³

et al. 2023

UEG Journal

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Acute severe ulcerative colitis (ASUC) occurs in up to 25% of patients with ulcerative colitis (UC). Therapeutic approaches have evolved during the past years with the increasing bio exposure of admitted patients and the extension of the number of approved drugs for UC. In this review, we aimed to summarize the latest evidence in short‐term and long‐term medical strategies for ASUC. In addition to general principles such as venous thromboembolism prophylaxis, screening for triggering and worsening factors and close monitoring, first‐line therapy for ASUC remains intravenous corticosteroids. In naive patients, the optimum maintenance strategy for steroid‐responding patients does not necessarily include biologics. Second‐line therapy includes infliximab or calcineurin inhibitors (CNIs) with similar short‐ and long‐term colectomy rates. Despite its pathophysiological relevance, there is insufficient evidence to promote intensified induction with infliximab. Prior treatment exposure is a cornerstone for guiding therapeutic choice of short‐ and long‐term therapies in the context of ASUC: in anti‐TNF exposed patients, CNIs may be favored as a bridge therapy to vedolizumab or ustekinumab. Third‐line salvage therapy could be a therapeutic option in selected patients referred to expert centers. Additionally, evidence is accumulating regarding the use of tofacitinib in ASUC.

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“…In addition, the approach of using probiotics has been adopted in multiple instances with encouraging results both in animal and human studies but never in the presence of cyclosporine [ 10 ]. Cyclosporine A (CyA), an immunosuppressant that interacts with cytoplasmic cyclophilin A (CypA) [ 11 , 12 ], was introduced in the mid-1980s. In addition, probiotics have been used in the last two decades to correct dysbiosis [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

The Mechanism and Potential Therapeutic Effects of Cyclosporin, Cyclophilin, Probiotics and Syndecan-1 in an Animal Model of Inflammatory Bowel Disease

Dosh,

Rappa,

Jurjus

et al. 2024

Pharmaceutics

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Background: Inflammatory bowel diseases (IBDs) have several treatment modalities including immunoregulators, like cyclosporine A, an immunosuppressant that interacts with cytoplasmic cyclophilin A, and probiotics. Aims: This study explored and compared the possible role of syndecan-1 in the IBD pathogenic process as well as the effectiveness of cyclophilin A, cyclosporine A, and their combination in the management of IBDs in the presence of probiotics. Methodology: IBD was induced in a total of 112 mice equally divided between syndecan-1 knock-out (KO) and Balb/c wild-type mice, using 2% dextran sulfate sodium (DSS) followed by intraperitoneal treatment with cyclosporine A, cyclophilin A, or a combination of both. In addition, a daily dose of probiotics was given in their drinking water. The animals were monitored for clinical signs and symptoms and checked for gross pathologies in the abdomen after 3 weeks. Descending and sigmoid colon biopsies were collected and fixed for routine microscopy or frozen for protein extraction and molecular testing for IL-6, CD3, CD147, and beta 1 integrins as well as pAkt expression. Results: The data showed that the induction of IBD in the syndecan-1 KO mice was more severe at the clinical, histological, and molecular levels than in the wild type. The combined CypA-CyA treatment showed no added inhibitory effect compared to single-drug treatment in both strains. Probiotics added to the combination was more effective in the wild type and, when used alone, its inhibition of IL-6 was the highest. As for the CD147 marker, there were more suppressions across the various groups in the KO mice except for the probiotics-alone group. Concerning CD3, it was significantly increased by the CypA-CyA complex, which led to more inflammation in the KO mice. Probiotics had little effect with the combination. In relation to beta 1 integrins, the CypA-CyA combination made no significant difference from CyA alone, and adding probiotics to the combination resulted in higher beta 1 integrin expression in the KO mice. As for pAkt, it was very well expressed and upregulated in both strains treated with DSS, but the effect was much larger in the KO mice. In brief, the CypA-CyA complex showed a decrease in the expression of pAkt, but there was no added effect of both drugs. Probiotics along with the complex had a similar reduction effects in both strains, with a greater effect in the wild-type mice, while probiotics alone led to a similar reduction in pAkt expressions in both strains. Conclusions: The differential effects of CyA, CypA, probiotics, and their combinations on the various inflammatory markers, as well as the histological alterations and clinical signs and symptoms, speak in favor of a clear role of syndecan-1 in reducing inflammation. However, probiotics need to be considered after more explorations into the mechanisms involved in the presence of CypA and CyA especially since pAkt is less active in their presence.

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A Prospective Trial with Long Term Follow-up of Patients With Severe, Steroid-Resistant Ulcerative Colitis Who Received Induction Therapy With Cyclosporine and Were Maintained With Vedolizumab

Cited by 12 publications

References 19 publications

In-hospital management of inflammatory bowel disease

In-hospital management of inflammatory bowel disease

Review article: Updated management of acute severe ulcerative colitis: From steroids to novel medical strategies

The Mechanism and Potential Therapeutic Effects of Cyclosporin, Cyclophilin, Probiotics and Syndecan-1 in an Animal Model of Inflammatory Bowel Disease

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