TY - JOUR
T1 - Early Change in Epithelial Neutrophilic Infiltrate Predicts Long-Term Response to Biologics in Ulcerative Colitis
AU - Narula, Neeraj
AU - Wong, Emily C.L.
AU - Colombel, Jean Frederic
AU - Riddell, Robert
AU - Marshall, John K.
AU - Reinisch, Walter
AU - Dulai, Parambir S.
N1 - Funding Information:
Conflicts of interest These authors disclose the following: Neeraj Narula has received honoraria from Janssen, AbbVie, Takeda, Pfizer, Merck, Sandoz, Novartis, and Ferring; Jean-Frederic Colombel has received research grants from AbbVie, Janssen Pharmaceuticals, and Takeda, payment for lectures from AbbVie, Amgen, Allergan, Inc, Ferring Pharmaceuticals, Shire, and Takeda, consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene Corporation, Celltrion, Eli Lilly, Enterome, Ferring Pharmaceuticals, Genentech, Janssen Pharmaceuticals, Landos, Ipsen, Medimmune, Merck, Novartis, Pfizer, Shire, Takeda,Tigenix, and Viela bio, and holds stock options in Intestinal Biotech Development and Genfit; John K. Marshall has received honoraria from Janssen, AbbVie, Allergan, Bristol-Meyer-Squibb, Ferring, Janssen, Lilly, Lupin, Merck, Pfizer, Pharmascience, Roche, Shire, Takeda, and Teva; Walter Reinisch has received speaker fees from Abbott Laboratories, AbbVie, Aesca, Aptalis, Astellas, Centocor, Celltrion, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Immundiagnostik, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka, PDL, Pharmacosmos, PLS Education, Schering-Plough, Shire, Takeda, Therakos, Vifor, and Yakult, has consulted for Abbott Laboratories, AbbVie, Aesca, Algernon, Amgen, AM Pharma, AMT, AOP Orphan, Arena Pharmaceuticals, Astellas, Astra Zeneca, Avaxia, Roland Berger GmBH, Bioclinica, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Covance, Danone Austria, DSM, Elan, Eli Lilly, Ernest & Young, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Gilead, Grünenthal, ICON, Index Pharma, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, LivaNova, Mallinckrodt, Medahead, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nash Pharmaceuticals, Nestle, Nippon Kayaku, Novartis, Ocera, OMass, Otsuka, Parexel, PDL, Periconsulting, Pharmacosmos, Philip Morris Institute, Pfizer, Procter & Gamble, Prometheus, Protagonist, Provention, Robarts Clinical Trial, Sandoz, Schering-Plough, Second Genome, Seres Therapeutics, Setpointmedical, Sigmoid, Sublimity, Takeda, Therakos, Theravance, Tigenix, UCB, Vifor, Zealand, Zyngenia, and 4SC, and has served as an advisory board member for Abbott Laboratories, AbbVie, Aesca, Amgen, AM Pharma, Astellas, Astra Zeneca, Avaxia, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Danone Austria, DSM, Elan, Ferring, Galapagos, Genentech, Grünenthal, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestle, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Sandoz, Schering-Plough, Second Genome, Setpointmedical, Takeda, Therakos, Tigenix, UCB, Zealand, Zyngenia, and 4SC; and Parmabir S. Dulai has received research support and consulting fees from Takeda, AbbVie, Janssen, and Pfizer. Supported by a McMaster University Department of Medicine Internal Career Award (N.N.); and by National Institutes of Health Digestive Diseases Research Center grant DK120515 and a Research Scholar Award from the American Gastroenterology Association (P.S.D.). The remaining authors disclose no conflicts.
Publisher Copyright:
© 2022 AGA Institute
PY - 2022/5
Y1 - 2022/5
N2 - Background & Aims: The prognostic value of histologic scores, grades, and individual histologic subcomponents, alone or in combination with endoscopy, for predicting endoscopic improvement (EI) and histoendoscopic mucosal improvement (HEMI) during maintenance therapy in ulcerative colitis remains uncertain. Methods: We performed a post hoc analysis of participants from the VARSITY trial (n = 734 with histology). Receiver operating characteristic and multivariate logistic regression analyses were performed to assess whether baseline and/or week 14 assessments for the Robarts Histopathology Index, Geboes score, individual histologic subcomponents, and baseline disease characteristics, including endoscopic severity and biomarkers, could predict the achievement of EI and HEMI at week 52. Results: Changes in epithelial neutrophil involvement from baseline to week 14 had the best performance for predicting week 52 EI (area under the curve, 0.83; 95 % confidence interval [CI], 0.74–0.91) and HEMI (area under the curve, 0.85; 95 % CI, 0.76–0.94). On multivariate analyses, improvement of neutrophils in the epithelium was the only histologic parameter associated with increased odds of week 52 EI (odds ratio, 3.63; 95 % CI, 1.45–9.08; P =.0059) and HEMI (odds ratio, 6.88; 95 % CI, 3.29–14.36; P <.0001). Patients with more than 50 % of crypts involved with neutrophils at week 14 were significantly less likely to achieve week 52 HEMI irrespective of week 14 Mayo endoscopic scores (week 14 Mayo endoscopic score of 2–3: 9.9 % vs 22.4 %; P =.001; week 14 Mayo endoscopic score of 0–1: 33 % vs 62.4 %; P =.044). Conclusions: Our results on epithelial neutrophilic infiltrate after induction therapy as the only independent predictor for achievement of maintenance EI or HEMI helps clarify the clinical relevance of measuring histologic disease activity in ulcerative colitis. Epithelial neutrophilic infiltrate poses a means to stratify patients according to their likelihood of response to biologic treatment.
AB - Background & Aims: The prognostic value of histologic scores, grades, and individual histologic subcomponents, alone or in combination with endoscopy, for predicting endoscopic improvement (EI) and histoendoscopic mucosal improvement (HEMI) during maintenance therapy in ulcerative colitis remains uncertain. Methods: We performed a post hoc analysis of participants from the VARSITY trial (n = 734 with histology). Receiver operating characteristic and multivariate logistic regression analyses were performed to assess whether baseline and/or week 14 assessments for the Robarts Histopathology Index, Geboes score, individual histologic subcomponents, and baseline disease characteristics, including endoscopic severity and biomarkers, could predict the achievement of EI and HEMI at week 52. Results: Changes in epithelial neutrophil involvement from baseline to week 14 had the best performance for predicting week 52 EI (area under the curve, 0.83; 95 % confidence interval [CI], 0.74–0.91) and HEMI (area under the curve, 0.85; 95 % CI, 0.76–0.94). On multivariate analyses, improvement of neutrophils in the epithelium was the only histologic parameter associated with increased odds of week 52 EI (odds ratio, 3.63; 95 % CI, 1.45–9.08; P =.0059) and HEMI (odds ratio, 6.88; 95 % CI, 3.29–14.36; P <.0001). Patients with more than 50 % of crypts involved with neutrophils at week 14 were significantly less likely to achieve week 52 HEMI irrespective of week 14 Mayo endoscopic scores (week 14 Mayo endoscopic score of 2–3: 9.9 % vs 22.4 %; P =.001; week 14 Mayo endoscopic score of 0–1: 33 % vs 62.4 %; P =.044). Conclusions: Our results on epithelial neutrophilic infiltrate after induction therapy as the only independent predictor for achievement of maintenance EI or HEMI helps clarify the clinical relevance of measuring histologic disease activity in ulcerative colitis. Epithelial neutrophilic infiltrate poses a means to stratify patients according to their likelihood of response to biologic treatment.
KW - Endoscopic Remission
KW - Histologic Remission
KW - Inflammatory Bowel Disease
KW - Neutrophils
KW - Ulcerative Colitis
UR - http://www.scopus.com/inward/record.url?scp=85114742771&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85114742771&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2021.07.005
DO - 10.1016/j.cgh.2021.07.005
M3 - Article
C2 - 34229037
AN - SCOPUS:85114742771
SN - 1542-3565
VL - 20
SP - 1095-1104.e9
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 5
ER -