title: Glucocorticoid bioactivity does not predict response to steroid therapy in severe pediatric ulcerative colitis.
abstract: BACKGROUND
  The pathophysiological basis for corticosteroid (CS) failure in ulcerative colitis (UC) is unknown. A transactivation glucocorticoid bioassay (GBA) was developed to measure the biological activity of CS by quantifying glucocorticoid response elements. This approach eliminates differences in bioavailability, chemistry, affinity, and other potential differences between the various steroids regarding their ability to activate the glucocorticoid receptor. In this multicenter prospective study, we aimed to evaluate whether CS bioavailability plays a role in CS refractoriness in severe pediatric UC.
  
  
  METHODS
  GBA (using COS-1 transfected cells) was measured in the serum of 50 children (52% males, age 13.4 +/- 3.5 years) admitted for acute severe UC on the third day of CS treatment. Demographic, clinical, and laboratory data were prospectively recorded.
  
  
  RESULTS
  Of the children enrolled, 16 (32%) failed CS therapy and required infliximab (n = 14) or colectomy (n = 2) within a median of 10 days (interquartile range [IQR] 6.5-14.5). Reflecting internal validity of the assay, GBA was highly correlated with the last CS dose and the time interval to bloodletting (r = -0.41 and r = -0.54, respectively; P < 0.001). There was no statistically significant difference in the GBA levels between responders and nonresponders (249 nM versus 200 nM cortisol equivalent, P = 0.18). In a multivariate regression model adjusted for time elapsed from CS and the administered dose, GBA did not predict response to CS (P = 0.34).
  
  
  CONCLUSIONS
  The lack of correlation of GBA level and treatment outcome lends support to the hypothesis that the bioavailability, type, and dosing of intravenous CS are not associated with response or failure to the drug.
authors.affiliation: Shaare Zedek Medical Center, Jerusalem, Israel. turnerd@szmc.org.il
authors.forename: Dan
authors.initials: D
authors.lastname: Turner
authors.forename: Kaija-Leena
authors.initials: KL
authors.lastname: Kolho
authors.forename: David R
authors.initials: DR
authors.lastname: Mack
authors.forename: Taneli
authors.initials: T
authors.lastname: Raivio
authors.forename: Neal
authors.initials: N
authors.lastname: Leleiko
authors.forename: Wallace
authors.initials: W
authors.lastname: Crandall
authors.forename: James
authors.initials: J
authors.lastname: Markowitz
authors.forename: Mark S
authors.initials: MS
authors.lastname: Silverberg
authors.forename: Olli A
authors.initials: OA
authors.lastname: Jänne
authors.forename: Joanne
authors.initials: J
authors.lastname: Stempak
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hyams
authors.forename: Anne M
authors.initials: AM
authors.lastname: Griffiths
mesh_terms: D000293:Adolescent; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001681:Biological Assay / Q000379:methods* / Q000592:standards; D019556:COS Cells; D002648:Child; D002522:Chlorocebus aethiops; D003082:Colectomy; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000276:immunology* / Q000601:surgery; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000097:blood / Q000276:immunology; D006760:Hospitalization; D006801:Humans; D000069285:Infliximab; D007275:Injections, Intravenous; D008297:Male; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012044:Regression Analysis; D015203:Reproducibility of Results
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D005938:Glucocorticoids; D000069285:Infliximab