Serum immune profiling in pediatric Crohn's disease demonstrates stronger immune modulation with first-line infliximab than conventional therapy and pre-treatment profiles predict clinical response to both treatments.

Abstract

Despite its efficacy, rational guidance for starting/stopping first-line biologic treatment in individual pediatric Crohn's disease (CD) patients is needed. We assessed how serum immune profiles before and after first-line infliximab (FL-IFX) or conventional (CONV) induction therapy associate with disease remission at week 52. pre- (n=86), and 10-14 week post-treatment (n=84) sera were collected from patients with moderate-to-severe paediatric CD in the TISKids trial, randomised to FL-IFX (n=48; five 5mg/kg infusions over 22 weeks) or CONV (n=43; exclusive enteral nutrition or oral prednisolone); both groups received azathioprine maintenance. The relative concentrations of 92 inflammatory proteins were determined with Olink Proteomics; fold changes (FC) with |Log2FC|>0.5 after FDR adjustment were considered significant. FL-IFX modulated a larger number of inflammatory proteins and induced stronger suppression than CONV; 18/30 proteins modulated by FL-IFX were not regulated by CONV. Hierarchical clustering based on IFX-modulated proteins at baseline revealed two clusters of patients: CD-hi patients had significantly higher concentrations of 23/30 IFX-modulated proteins (including oncostatin-M, TNFSF14, HGF, TGF-α) and higher clinical disease activity, CRP and blood neutrophils at baseline than CD-lo patients. Only 24% of CD-hi FL-IFX-treated patients maintained remission without escalation at week 52 vs 58% of CD-lo FL-IFX-treated patients. Similarly, 6% of CD-hi CONV-treated patients achieved remission vs 20% of CONV-treated CD-lo patients. Clustering based on immune profiles post-induction therapy did not relate to remission at week 52. FL-IFX leads to stronger reductions and modulates more immune proteins than CONV. Stratification on pre-treatment profiles of IFX-modulated proteins directly relates to maintenance of remission without treatment escalation.