Exploration of predictive biomarkers of early infliximab response in acute severe colitis: A prospective pilot study.
J Crohns Colitis. 2017 Nov 07;:
Authors: Beswick L, Rosella O, Rosella G, Headon B, Sparrow MP, Gibson PR, van Langenberg DR
Background: Outcomes of acute severe ulcerative colitis (ASUC) appear dependent on early intervention with the first and/or further infliximab(IFX) doses, though parameters to guide decision-making remain uncertain.
Aim: To assess whether serum/faecal IFX levels and inflammatory biomarkers early post-IFX dose can predict ASUC outcomes.
Methods: This prospective pilot study consecutively recruited inpatients with steroid-refractory ASUC, who then received 1-3 IFX rescue doses (5mg/kg/dose) per treating clinician’s discretion. Serum IFX, CRP, albumin and faecal calprotectin(FC) concentrations were measured daily as inpatient, then 7, 14, 28, 42d post-first IFX. Faecal IFX was measured one day post-IFX. Primary endpoint was clinical remission (partial Mayo(PM)=0) and CRP ≤3mg/L at 6w. Secondary endpoints were 12w clinical remission or colectomy during follow-up.
Results: Of 24 ASUC patients with median follow-up 28m (range 13,44), 10(42%) achieved remission at 6w, 12(50%) achieved 12w remission, 6(25%) had colectomy. 97% received either 2 or 3 IFX doses. Post-first dose, receiver-operator curve derived cutoffs of area-under-curve (AUC, days 4-7) concentrations for serum IFX, FC and PM scores each predicted the primary endpoint with 100% sensitivity, and predicted future colectomy with 89-94% sensitivity. In multivariate analyses, faecal IFX >1ug/g (OR 0.04 [0.2,0.9]), PM AUCd1-3<20 (OR 20.2 [1.01,404], each p<0.05), FC AUCd1-3<10000ug/ml (OR 13.6 [0.6, 294], trend only, p=0.09) were each associated with clinical and CRP remission(6w).
Conclusions: In ASUC, post-first dose IFX, early assessment of serum/faecal IFX, calprotectin and partial Mayo scores can accurate predict future remission and colectomy, thus potentially aid decision-making, i.e. accelerated IFX dosing or surgical planning if/when needed.
PMID: 29121178 [PubMed – as supplied by publisher]