TY - JOUR
T1 - Exploration of predictive biomarkers of early infliximab response in acute severe colitis
T2 - A prospective pilot study
AU - Beswick, Lauren
AU - Rosella, Ourania
AU - Rosella, Gennaro
AU - Headon, Belinda
AU - Sparrow, Miles P.
AU - Gibson, Peter R.
AU - van Langenberg, Daniel R.
PY - 2018/3
Y1 - 2018/3
N2 - Background: The outcomes of acute severe ulcerative colitis [ASUC] appear to be dependent on early intervention with the first and/or further infliximab [IFX] doses, although parameters to guide decision-making remain uncertain. Aim: To assess whether serum/faecal IFX levels and inflammatory biomarkers early after 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 [5 mg/kg per dose] at the discretion of the treating clinician. Serum IFX, C-reactive protein [CRP], albumin and faecal calprotectin [FC] concentrations were measured daily as an inpatient, and then 7, 14, 28 and 42 days post-first IFX. Faecal IFX was measured 1 day post-IFX. The primary end point was clinical remission (partial Mayo [PM] = 0) and CRP ≤3 mg/l at 6 weeks. Secondary end points were 12-week clinical remission or colectomy during follow-up. Results: Of 24 ASUC patients with a median follow-up of 28 months [range 13-44], 10 [42%] achieved remission at 6 weeks, 12 [50%] achieved 12-week remission, six [25%] had colectomy. In total, 97% received either two or three IFX doses. Post-first dose, receiver-operator curvederived cutoffs of the area-under-curve [AUC, Days 4-7] concentrations for serum IFX, FC and PM scores each predicted the primary end point with 100% sensitivity, and predicted future colectomy with 89-94% sensitivity. In multivariate analyses, faecal IFX > 1 μg/g (odds ratio [OR] 0.04 [0.2, 0.9]), PM AUCd1-3 < 20 (OR 20.2 [1.01, 404], each P < 0.05), FC AUCd1-3 < 10 000 μg/ml [OR 13.6 [0.6, 294], trend only, p = 0.09) were each associated with clinical and CRP remission [6 weeks]. Conclusions: In ASUC, post-first dose IFX, early assessment of serum/faecal IFX, calprotectin and PM scores can accurately predict future remission and colectomy, and thus potentially aid in decision-making, i.e. accelerated IFX dosing or surgical planning if/when needed.
AB - Background: The outcomes of acute severe ulcerative colitis [ASUC] appear to be dependent on early intervention with the first and/or further infliximab [IFX] doses, although parameters to guide decision-making remain uncertain. Aim: To assess whether serum/faecal IFX levels and inflammatory biomarkers early after 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 [5 mg/kg per dose] at the discretion of the treating clinician. Serum IFX, C-reactive protein [CRP], albumin and faecal calprotectin [FC] concentrations were measured daily as an inpatient, and then 7, 14, 28 and 42 days post-first IFX. Faecal IFX was measured 1 day post-IFX. The primary end point was clinical remission (partial Mayo [PM] = 0) and CRP ≤3 mg/l at 6 weeks. Secondary end points were 12-week clinical remission or colectomy during follow-up. Results: Of 24 ASUC patients with a median follow-up of 28 months [range 13-44], 10 [42%] achieved remission at 6 weeks, 12 [50%] achieved 12-week remission, six [25%] had colectomy. In total, 97% received either two or three IFX doses. Post-first dose, receiver-operator curvederived cutoffs of the area-under-curve [AUC, Days 4-7] concentrations for serum IFX, FC and PM scores each predicted the primary end point with 100% sensitivity, and predicted future colectomy with 89-94% sensitivity. In multivariate analyses, faecal IFX > 1 μg/g (odds ratio [OR] 0.04 [0.2, 0.9]), PM AUCd1-3 < 20 (OR 20.2 [1.01, 404], each P < 0.05), FC AUCd1-3 < 10 000 μg/ml [OR 13.6 [0.6, 294], trend only, p = 0.09) were each associated with clinical and CRP remission [6 weeks]. Conclusions: In ASUC, post-first dose IFX, early assessment of serum/faecal IFX, calprotectin and PM scores can accurately predict future remission and colectomy, and thus potentially aid in decision-making, i.e. accelerated IFX dosing or surgical planning if/when needed.
KW - Colectomy
KW - Infliximab
KW - Ulcerative colitis
UR - http://www.scopus.com/inward/record.url?scp=85046068473&partnerID=8YFLogxK
U2 - 10.1093/ecco-jcc/jjx146
DO - 10.1093/ecco-jcc/jjx146
M3 - Article
C2 - 29121178
AN - SCOPUS:85046068473
SN - 1873-9946
VL - 12
SP - 289
EP - 297
JO - Journal of Crohn's and Colitis
JF - Journal of Crohn's and Colitis
IS - 3
ER -