Fecal calprotectin, lactoferrin, and endoscopic disease activity in monitoring anti-TNF-alpha therapy for Crohn's disease.
BACKGROUND
Fecal calprotectin and lactoferrin are promising noninvasive biomarkers for intestinal inflammation. In Crohn's disease (CD), during anti-TNF-alpha (TNF-alpha) treatment, the clinical significance of these markers has, however, been insufficiently explored.


METHODS
Among CD patients receiving anti-TNF-alpha therapy we assessed the role of fecal calprotectin and lactoferrin as surrogate markers for mucosal healing. Before and 3 months after the beginning of anti-TNF-alpha induction, 15 patients underwent ileocolonoscopy with scoring of the Crohn's Disease Index of Severity (CDEIS). Fecal samples for calprotectin and for lactoferrin measurements were collected and the Crohn's Disease Activity Index (CDAI) was calculated at the time of the endoscopies and 2 and 8 weeks after the first treatment.


RESULTS
The median CDEIS fell from 13.0 to 4.8 (P = 0.002) and CDAI from 158 to 68 (P = 0.005). Accordingly, the median fecal calprotectin concentration fell from 1173 microg/g to 130 microg/g (P = 0.001) and fecal lactoferrin from 105.0 microg/g to 2.7 microg/g (P = 0.001). Of the 15 patients, 11 (73%) showed an endoscopic response to treatment and 5 of these achieved endoscopic remission (CDEIS < 3). In those 5 patients the fecal calprotectin concentration declined from 1891 mug/g (range 813-2434) to 27 microg/g (13-130) and lactoferrin from 92.4 microg/g (35.5-235.6) to 1.9 microg/g (0.0-2.1).


CONCLUSIONS
Compared to pretreatment values, concentrations of fecal calprotectin and lactoferrin after the anti-TNF-alpha treatment were significantly lower. During anti-TNF-alpha therapy these fecal neutrophil-derived proteins may thus be useful surrogate markers for mucosal healing.
Sipponen
Taina
T
Department of Medicine, Division of Gastroenterology, Helsinki University Central Hospital, Helsinki, Finland. taina.sipponen@kolumbus.fi
Savilahti
Erkki
E
Kärkkäinen
Päivi
P
Kolho
Kaija-Leena
KL
Nuutinen
Hannu
H
Turunen
Ulla
U
Färkkilä
Martti
M
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D003424:Crohn Disease / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D016099:Endoscopy, Gastrointestinal / Q000379:methods*; D005243:Feces / Q000737:chemistry*; D005260:Female; D006801:Humans; D007781:Lactoferrin / Q000032:analysis*; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis*; D008297:Male; D011379:Prognosis; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
D015415:Biomarkers; D039841:Leukocyte L1 Antigen Complex; D014409:Tumor Necrosis Factor-alpha; D007781:Lactoferrin