G. Frieri et al., Prevention of post-operative recurrence of Crohn's disease requires adequate mucosal concentration of mesalazine, ALIM PHARM, 13(5), 1999, pp. 577-582
Background: Surgical resection of Crohn's disease is followed by early recu
rrence in a high percentage of patients, Mesalazine has been shown to be ef
fective in the prevention of post-operative recurrence, but some 50% of pat
ients under treatment recur at 3 years of follow-up,
Aim: To establish whether the mucosal concentration of mesalazine might aff
ect the development of post-operative recurrence.
Methods: Colon-ileoscopy was performed in 25 consecutive patients resected
for Crohn's disease. The mean time from surgery was 14 months. After the op
eration, all patients were taking oral mesalazine (Asacol, 2.4 g/day), Ten
patients showed signs of endoscopic recurrence (apthae, ulcers, narrowing o
f the lumen) in the neoterminal ileum, five of whom also showed juxta-anast
omotic colonic involvement. Fifteen patients were free of recurrence. At en
doscopy, four biopsies were taken from the perianastomotic area (two specim
ens at the ileal site and two specimens at the colonic site of the anastomo
sis), The specimens were weighed and immediately frozen at -80 degrees C. M
esalazine concentration (ng/mg) was measured in tissue homogenates by highp
erformance liquid chromatography with elcctrochemical detection. Fisher's e
xact test was used for the statistical analysis,
Results: The mean value of mucosal mesalazine concentration, expressed as n
g/mg of tissue, was significantly lower in patients with recurrence than in
those without recurrence both in the ileum (mean +/- s.d.: 21.6 +/- 28.3 v
s. 70.9 +/- 47.4: P = 0.007) and in the colon (25.8 +/- 26.4 vs, 60.3 +/- 3
2.5: P = 0.010),
Conclusions: The mucosal conentration of mesalazine in the juxta-anastomati
c area is significantly lower in patients with recurrence than in those fre
e of recurrence. These data could suggest an association between mucosal me
salazine concentrations and the clinical effectiveness of the drug.