Calcineurin Inhibitors in Ulcerative Colitis

2017 ◽  
pp. 421-428
Author(s):  
Andreas Fischer ◽  
Daniel C. Baumgart
Keyword(s):  
Ulcerative Colitis ◽  
Calcineurin Inhibitors

scholarly journals P445 Efficacy and safety of induction therapy with calcineurin inhibitors followed by maintenance therapy with vedolizumab in severe ulcerative colitis: a large patient cohort with long-term follow-up

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S401-S401
Author(s):  
J OLLECH ◽  
S Dwadasi ◽  
I Normatov ◽  
A Israel ◽  
V Rai ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Maintenance Therapy ◽  
Median Time ◽  
Induction Therapy ◽  
Calcineurin Inhibitor ◽  
Calcineurin Inhibitors ◽  
Free Survival ◽  
Severe Ulcerative Colitis ◽  
Steroid Refractory

Abstract Background The options for the medical management of patients with severe ulcerative colitis failing IV steroids are limited and include the calcineurin inhibitors cyclosporin or tacrolimus, especially in patients who had previously failed anti-TNF agents. Following induction therapy with a calcineurin inhibitor, transitioning to vedolizumab as maintenance therapy could be an option. We report on the largest cohort of patients successfully induced with calcineurin inhibitors who were then transitioned to vedolizumab maintenance therapy. Methods We performed a retrospective observational study of adult ulcerative colitis patients followed at the University of Chicago Inflammatory Bowel Disease Center. Patients with severe steroid-refractory ulcerative colitis were included if they received a calcineurin inhibitor (ciclosporin or tacrolimus) as induction therapy followed by maintenance therapy with vedolizumab between January 2014 and December 2018. Patients who had a follow-up of fewer than three months were excluded. The primary endpoint was colectomy-free survival. Secondary endpoints included survival without vedolizumab discontinuation as well as clinical, steroid-free and biochemical remission at week 14. Results A total of 71 patients (59% male) were treated with vedolizumab after induction therapy with calcineurin inhibitors for severe steroid-refractory colitis. Truelove and Witts criteria for Acute Severe Ulcerative Colitis were fulfilled in 77% of patients, and 97% of patients had moderate to severe endoscopic disease. Patients were followed for a median time of 25 months (IQR 16–36). Colectomy free survival rates from vedolizumab initiation were 67% at one year and 55% at two years (Figure 1, Panel A). At the end of induction with vedolizumab at week 14, 50% of patients were in clinical remission, and 62% of patients had a normal CRP. At one and two years following vedolizumab initiation, 43% and 28% of patients were still on vedolizumab, respectively (Figure 1, Panel B). Vedolizumab was dose escalated to infusions every four weeks in 44% of patients. The median time to dose escalation was 5.6 months (IQR 4.1–8.2). No serious adverse events were recorded in our patient cohort. Conclusion Transitioning to vedolizumab following induction of remission with calcineurin inhibitors is effective and safe. Such a treatment strategy should be considered in patients with severe steroid-refractory ulcerative colitis, especially in cases of previous anti-TNF failure.

scholarly journals EFFICACY OF TACROLIMUS FOR INDUCTION OF REMISSION IN PATIENTS WITH MODERATE-TO-SEVERE ULCERATIVE COLITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

2017 ◽  
Vol 54 (2) ◽  
pp. 167-172 ◽  
Author(s):  
Juan LASA ◽  
Pablo OLIVERA
Keyword(s):  
Systematic Review ◽  
Ulcerative Colitis ◽  
Clinical Response ◽  
Clinical Efficacy ◽  
Lower Risk ◽  
Meta Analysis ◽  
Calcineurin Inhibitors ◽  
Cochrane Library ◽  
Severe Ulcerative Colitis ◽  
Risk Of Failure

ABSTRACT BACKGROUND There is evidence that shows that calcineurin inhibitors may be useful for the treatment of severe ulcerative colitis. However, evidence regarding the efficacy of tacrolimus for remission induction in this setting is scarce. OBJECTIVE To develop a systematic review on the existing evidence regarding the clinical efficacy of tacrolimus for the induction of remission in patients with moderate-to-severe ulcerative colitis. METHODS A literature search was undertaken from 1966 to August 2016 using MEDLINE, Embase, LILACS and the Cochrane Library. The following MeSH terms were used: “Inflammatory Bowel Diseases” or “Ulcerative Colitis” and “Calcineurin Inhibitors” or “Tacrolimus” or “FK506”. Studies performed in adult ulcerative colitis patients that evaluated the clinical efficacy of tacrolimus for the induction of remission were considered for revision. A meta-analysis was performed with those included studies that were also placebo-controlled and randomized. Clinical response as well as clinical remission and mucosal healing were evaluated. RESULTS Overall, 755 references were identified, from which 22 studies were finally included. Only two of them were randomized, placebo-controlled trials. A total of 172 patients were evaluated. A significantly lower risk of failure in clinical response was found for tacrolimus versus placebo [RR 0.58 (0.45-0.73)]; moreover, a lower risk of failure in the induction of remission was also found versus placebo [RR 0.91 (0.82-1)]. CONCLUSION Tacrolimus seems to be a valid therapeutic alternative for the induction of remission in patients with moderate-to-severe ulcerative colitis.

Short- and long-term efficacy of adalimumab salvage therapy after failure of calcineurin inhibitors in steroid-refractory ulcerative colitis

2018 ◽  
Vol 53 (10-11) ◽  
pp. 1236-1244 ◽  
Author(s):  
Masafumi Nishio ◽  
Yoshito Ishii ◽  
Yu Hashimoto ◽  
Haruka Otake ◽  
Tsuyoshi Ogashiwa ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Salvage Therapy ◽  
Calcineurin Inhibitors ◽  
Term Efficacy ◽  
Short And Long Term ◽  
Steroid Refractory

scholarly journals Treatment of severe acute ulcerative colitis in SARS-CoV-2 infected patients: report of three cases and discussion of treatment options

2021 ◽  
Vol 14 ◽  
pp. 175628482110125
Author(s):  
Arno R. Bourgonje ◽  
Reinier C. A. van Linschoten ◽  
Rachel L. West ◽  
Maarten A. van Dijk ◽  
Coretta C. van Leer-Buter ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Decision Making ◽  
Treatment Options ◽  
Calcineurin Inhibitors ◽  
Future Research ◽  
Immunomodulatory Drugs ◽  
Therapeutic Decision ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Therapeutic Decision Making

In the wake of the coronavirus disease 2019 (COVID-19) pandemic, it is unclear how asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected patients who present with acute severe ulcerative colitis (UC) can be treated effectively and safely. Standard treatment regimens consist of steroids, immunomodulatory drugs, and biological therapies, but therapeutic decision-making becomes challenging as there are uncertainties about how to deal with these drugs in patients with COVID-19 and active UC. Importantly, guidelines for this particular group of patients with UC are still lacking. To inform therapeutic decision-making, we describe three consecutive cases of patients with active UC and COVID-19 and discuss their treatments based on theoretical knowledge, currently available evidence and clinical observations. Three patients were identified through our national inflammatory bowel disease network [Initiative on Crohn’s and Colitis (ICC)] for whom diagnosis of SARS-CoV-2-infection was established by reverse transcription–polymerase chain reaction (RT-PCR) testing in nasopharynx, stools, and/or biopsies. Acute severe UC was diagnosed by clinical parameters, endoscopy, and histopathology. Clinical guidelines for SARS-CoV-2-negative patients advocate the use of steroids, calcineurin inhibitors, or tumor necrosis factor alpha (TNF-α)-antagonists as induction therapy, and experiences from the current three cases show that steroids and TNF-α-antagonists could also be used in patients with COVID-19. This could potentially be followed by TNF-α-antagonists, vedolizumab, or ustekinumab as maintenance therapy in these patients. Future research is warranted to investigate if, and which, immunomodulatory drugs should be used for COVID-19 patients that present with active UC. To answer this question, it is of utmost importance that future cases of patients with UC and COVID-19 are documented carefully in international registries, such as the SECURE-IBD registry.

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