Outcome of tacrolimus and vedolizumab after corticosteroid and anti-TNF failure in paediatric severe colitis

Abstract

BackgroundSevere colitis flare from ulcerative colitis (UC) or Crohn’s disease (CD) may be refractory to corticosteroids and antitumour necrosis factor (TNF) agents resulting in high colectomy rates. We aimed to describe the utility of tacrolimus to prevent colectomy during second-line vedolizumab initiation after corticosteroid and anti-TNF treatment failure in paediatric severe colitis.MethodsA retrospective cohort analysis was performed between 1 October 2014 and 31 October 2016 at a single tertiary care centre. Inclusion criteria were patients with severe colitis who received tacrolimus before or during vedolizumab induction and previous exposure to anti-TNF therapy with or without corticosteroids. The initiation of tacrolimus was clinician dependent based on an institutional protocol.ResultsTwelve patients (10 UC, two CD; median age 16 years; three female) received at least one dose of vedolizumab 10 mg/kg (max of 300 mg) due to anti-TNF therapy failure and persistent flare not responsive to corticosteroids. Of the 12 patients, eight (67%) and four (33%) had failed one or two anti-TNF agents, respectively. Tacrolimus was initiated for acute disease severity during hospitalisation (58%) or ongoing flare during outpatient care (42%). 9 (75%) of 12 patients avoided colectomy or inflammatory bowel disease-related surgery at 24 weeks and eight (68%) continued on vedolizumab maintenance with no adverse events out to 80 weeks.ConclusionWe report real-world data on the outcome of tacrolimus around vedolizumab initiation in paediatric UC or CD after corticosteroid and anti-TNF therapy treatment failure. Our pilot experience indicates a potential benefit of concomitant tacrolimus when initiating vedolizumab therapy.

Safety and efficacy of vedolizumab in pediatric patients with ulcerative colitis: multicenter study in Japan

“…The efficacy and safety of VDZ for pediatric patients with IBD have been reported in relatively small case series 6–13 . Data S3 summarizes the previous reports about VDZ therapy in pediatric IBD.…”

Tacrolimus for ulcerative colitis in children: a multicenter survey in Japan

“…On the other hand, 15 patients with remission or response in the short-term effect were newly-bridged to azathioprine after tacrolimus, but only 1 patient could achieve remission after 1 year without rescue therapy. Thiopurine preparations alone may be insufficient to maintain long-term remission; however, it is possible that tacrolimus will be a useful bridge therapy for vedolizumab in future [4,23].…”

Management of Pediatric Patients Hospitalized with Crohn’s Disease

“…Consideration for possible surgery in the near future should be balanced against the potential benefit of vedolizumab. However, the use of tacrolimus has been proposed as a bridge to vedolizumab maintenance therapy which may help navigate this risk [25]. Hamel et al proposed concomitant initiation of tacrolimus and vedolizumab with initial goal tacrolimus troughs of 10-15 ng/dL and titration to 8-10 ng/dL once rectal bleeding has resolved [25].…”

“…However, the use of tacrolimus has been proposed as a bridge to vedolizumab maintenance therapy which may help navigate this risk [25]. Hamel et al proposed concomitant initiation of tacrolimus and vedolizumab with initial goal tacrolimus troughs of 10-15 ng/dL and titration to 8-10 ng/dL once rectal bleeding has resolved [25]. The additive risk of multiple immunosuppressive effects must be evaluated in the context of the risk of severe CD flares not responding to first-line therapy.…”