The Role of Serologic Markers in Identifying Infliximab Response in Ulcerative Colitis

Abstract

Purpose: The definition of colitis is evolving from the traditional two-disease model – ulcerative colitis (UC) and Crohn's disease (CD) – towards an immuno-inflammatory spectrum of disease. Molecular diagnostic tools, including serological markers for perinuclear anti-neutrophil cytoplasmic antibody (pANCA) which suggests more of a UC phenotype, as well as both anti-Saccharomyces cerevisiae antibody (ASCA) and outer membrane porin of Escherichia coli (OmpC) suggest more of a CD phenotype, hold promise for stratifying differing patterns of colitis. Furthermore, anti-CBir1 antibody helps distinguish between UC and CD in pANCA positive patients. While infliximab (IFX) is approved for the treatment of both CD and moderate to severe UC, approximately one third of UC patients do not respond. The primary objective is to assess whether serologic markers identify a subset of patients with UC who are likely to respond to infliximab therapy. Methods: We retrospectively reviewed those patients with UC who were treated with IFX from January 2002 to September 2006 and also were tested for serologic markers including ASCA, pANCA and OmpC. The Ulcerative Colitis Disease Activity Index (UCDAI) was calculated on all patients in a prospective manner. All patients included in the study underwent mucosal evaluation both prior to and following IFX treatment. The primary endpoint was response to infliximab, as defined by a 3-point improvement in the UCDAI. These patients were then stratified by pANCA and ASCA status. Regression analysis was performed to determine the predictive value of the serologies. Results: We analyzed a total of 11 patients, and 10/11 (91%) were pANCA positive. There were 7 patients who responded to IFX, with a with a mean decrease of UCDAI of 3.83 (range 3–5, P < 0.001). Of the responders, 42.9% (3/7) were ASCA (IgG and IgA) positive and 85.7% (6/7) were pANCA positive. Of the 6 patients who were pANCA positive, 33.3% (2/6) were also ASCA positive and 66.7% (4/6) were either ASCA and/or OmpC positive. The 4 patients who were IFX non-responders had no significant change in UCDAI (mean change in UCDAI of 0.5, P= 0.182) and all were only positive for pANCA with high titers. The combination of ASCA and OmpC together showed a trend towards infliximab response. Conclusion: Serologies in colitis patients suggesting a Crohn's phenotype – either ASCA positive alone or pANCA positive in combination with ASCA or OmpC – may identify an immunologically vulnerable subset who are likely to respond to anti-TNF therapy. Further study in a larger group of colitis patients with the addition of other markers, including anti-CBir1, to stratify therapeutic responses, is warranted.