Basic fibroblast growth factor as a response parameter to infliximab in fistulizing Crohn's disease.
BACKGROUND
Fibroblast growth factors play an important role in (patho)physiological processes such as wound healing and tissue repair. We previously showed that basic fibroblast growth factor is actively involved in inflammatory bowel disease processes. In the present retrospective study, we assessed whether serum basic fibroblast growth factor levels in Crohn's disease patients reflect the response to anti-tumour necrosis factor-alpha antibody infliximab treatment.


OBJECTIVE
Serum samples, biopsies and patient data from a subgroup of patients included in two placebo-controlled trials were used. Fistulizing Crohn's disease patients (n = 42) were administered placebo or infliximab intravenously three times and evaluated for response up to 18 weeks. Biopsies from a subgroup of patients were stained for basic fibroblast growth factor using indirect immunohistochemistry. In the active Crohn's disease trial, patients (n = 24) received either placebo or infliximab once, and disease activity and serum basic fibroblast growth factor were assessed at weeks 0 and 4.


RESULTS
Basic fibroblast growth factor levels at inclusion were comparable in the fistulizing Crohn's disease patients regardless of whether the fistulas did or did not respond or completely heal (median range: 9.3-10.6 pg/mL). At the end of follow-up basic fibroblast growth factor levels were lower in patients who responded (9.2 pg/mL, P = 0.06) or who were completely healed (8.9 pg/mL, P = 0.009) when compared with patients did not respond/heal (14.5 pg/mL), the latter not significantly increased from baseline. Decreases in the perianal disease activity index and open fistula scores at the end of the follow-up were significantly correlated with the decrease in basic fibroblast growth factor (R = 0.41; P = 0.012 and R = 0.35; P =0.027, respectively). Immunohistological evaluation also showed a trend towards decreased basic fibroblast growth factor expression in intestinal biopsies of these patients. Patients with active disease, i.e. a Crohn's disease activity index > or = 220 combined from the two studies, were found to have significantly (P = 0.0046) lower baseline serum basic fibroblast growth factors levels than those with inactive disease (5.3 vs. 10.3 pg/mL, respectively). Treatment of the active disease patients did not affect the serum basic fibroblast growth factor level, although a general decrease in disease activity was observed with infliximab treatment.


CONCLUSIONS
Healing of fistulizing/perianal Crohn's disease seems to be reflected by a decrease in high serum basic fibroblast growth factor. Basic fibroblast growth factor levels do not relate with response in active Crohn's disease patients.
Gao
Q
Q
Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
Hogezand
R A
RA
Lamers
C B H W
CB
Verspaget
H W
HW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003424:Crohn Disease / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood*; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D000069285:Infliximab; D007412:Intestinal Fistula / Q000097:blood / Q000150:complications*; D008297:Male; D008875:Middle Aged
D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D016222:Fibroblast Growth Factor 2; D000069285:Infliximab