Ciclosporin Therapy After Infliximab Failure in Hospitalized Patients With Acute Severe Colitis is Effective and Safe

Abstract

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background and Aims</jats:title> <jats:p>Options for medical management of patients with acute severe colitis [ASC] failing intravenous (i.v.) steroids are limited and include rescue therapy with either infliximab or ciclosporin. In patients failing infliximab, second-line rescue therapy with ciclosporin is an alternative. The aim of this study was to investigate the efficacy and safety of ciclosporin in patients with steroid-refractory ASC failing first-line rescue therapy with infliximab.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>This is a retrospective, tertiary centre study undertaken from 2010 to 2017. Included were patients hospitalized for ASC and treated with i.v. ciclosporin after failing i.v. steroids and infliximab within the previous 2 months. Time to colectomy, clinical response, and occurrence of adverse events were analysed.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Forty patients with steroid-resistant ASC were included. Patients were followed for a median of 13 months (interquartile range [IQR] 5–32 months). Colectomy-free survival was 65%, 59.4%, and 41.8% at 1 month, 3 months and 1 year, respectively. Sixty percent of patients [24/40] achieved clinical remission at a median of 2 weeks [IQR 1–3 weeks]. Infliximab levels before ciclosporin infusion were available for 26 patients [median level 17.5 mg/mL, IQR 8–34 mg/mL] and were not associated with adverse events. Sixteen patients [40%] experienced adverse events after ciclosporin treatment, but none resulted in drug discontinuation.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>In patients with i.v. steroid–refractory ASC who failed infliximab therapy, second-line rescue therapy with ciclosporin was shown to be effective and safe. This is the largest patient cohort to receive ciclosporin as second-line rescue therapy for ASC. We believe that ciclosporin may be offered to selected patients prior to referral for colectomy.</jats:p> </jats:sec>

Efficacy and safety of induction therapy with calcineurin inhibitors followed by vedolizumab maintenance in 71 patients with severe steroid‐refractory ulcerative colitis

“…The current study adds confidence to using the approach of inducing remission with CNIs-which are potent and fast-acting drugs with proven efficacy in treating patients with severe ulcerative colitis 3,[5][6][7][8]17,18,20 and then transitioning to the slower acting steroid-sparing agent, vedolizumab, for maintenance therapy. 9,10 We have shown that overlapping these two drugs is effective and safe.…”

“…Inducing remission with CNIs and transitioning to vedolizumab maintenance therapy is becoming more relevant as more patients with ulcerative colitis now have a history of previous exposure and failure to anti‐TNFs and azathioprine . Likewise, since the publication of the CYSIF and CONSTRUCT trials, which demonstrated similar short‐term response rates between infliximab and ciclosporin in the setting of acute severe ulcerative colitis, infliximab has emerged as the predominant agent used in such patients, and more patients are presenting to tertiary care centres after failing infliximab . A potential reason for nonresponse to infliximab is secondary loss of serum proteins due to monoclonal antibodies loss through an inflamed gut and in such patients, the use of a nonprotein‐based therapy for induction of remission, such as a CNI, could be useful.…”

“…Patients who are successfully induced with infliximab continue to maintenance therapy with this drug. Secondary to its increased use in ulcerative colitis, patients failing infliximab are becoming more prevalent …”

“…Secondary to its increased use in ulcerative colitis, patients failing infliximab are becoming more prevalent. 8 While highly effective at inducing remission in patients with ulcerative colitis, 3,5 protracted use of CNIs is limited by adverse events, including infection, nephrotoxicity, hypercholesterolaemia and hypertension. Consequently, their use in inflammatory bowel disease has been limited to induction therapy.…”

Management of Acute Severe Colitis in the Era of Biologicals and Small Molecules

“…Practically speaking, IFX is preferred as second-line therapy. Weisshof et al assessed 40 steroid and IFX-refractory ASUC patients receiving sequential therapy with CsA; 60% achieved clinical remission within 2 weeks, and 42% had colectomy-free survival at 1 year, with no increased in adverse events, which suggest CsA therapy following rescue therapy failure with IFX can be effective and safe in ASUC [56]. A recent publication in a mixed cohort of steroid and/or anti-TNF refractory UC +/− ASUC (n = 39) has shown safety and efficacy of bridging patients from third line CsA to VDZ, with 68% colectomy-free rate at 12 months follow-up [57].…”