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Fibrosis and strictures are common and irreversible complications of Crohn's disease that potentially necessitate bowel resection. Tranilast, N‐(3',4'‐dimethoxycinnamoyl) anthranilic acid, inhibits keloid scar formation through the inhibition of production of metalloproteinases and tissue inhibitor of metalloproteinase‐1 from neutrophils.1 Please check the phrase “inhibition of … neutrophils” is OK Tranilast has been shown to inhibit fibrosis in various experimental models.2,3,4 Randomised, double‐blind, placebo‐controlled studies have shown substantial inhibition by tranilast of restenosis of coronary arteries.5,6,7 A case report has demonstrated the efficacy of long‐term administration of tranilast in inflammatory endobronchial stenosis.8
Between June 2001 and July 2005, 24 patients with quiescent Crohn's disease with non‐symptomatic intestinal strictures were recruited. Baseline intestinal stricture was evaluated by small bowel barium enteroclysis, or Gastrografin® (Schering Aktiengesellschaft, Berlin, Germany) enteroclysis under endoscopic examination using a digital caliper (Digimatic® Caliper, Mitutoyo Corporation, Kawasaki, Japan). Patients were allocated using a random number table to receive tranilast 200 mg (2 tablets) after every meal, three times daily (tranilast group) or to a control group that did not receive the agent, and followed up prospectively. The primary endpoint was whether or not there was development of symptomatic stricture requiring hydrostatic balloon dilatation of the stricture or requiring surgical resection, which was quantified as the cumulative non‐symptomatic stricture rate. The secondary endpoint used in this study was the diameter of the stricture, which was measured at the time of recruitment (basal diameter) and at the time of development of symptomatic stricture or at the latest follow‐up (final diameter). Change in diameter during the follow‐up period was assessed using the equation (final diameter‐basal diameter/basal diameter) 100/month. The change in diameter was compared between groups (% change/month)
There was no significant difference in clinical backgrounds between the tranilast group and the control group (table 11).). One patient in the tranilast group withdrew because of a reduced white blood cell count. During the observation period, one patient in the tranilast group and two in the control group received infliximab infusion, and two tranilast and one control patient had been taking oral prednisolone. Six tranilast and seven control patients had been taking immunomodulators (azathioprine or mercaptopurine there were no significant differences between groups for these factors.
Hydrostatic balloon dilatation was done in one patient in the tranilast group and in five patients in the control group owing to the development of symptomatic stricture (fig 11,, p=0.0034). The median basal diameter of the stricture was 6.40 mm (25th percentile 4.25, 75th percentile 6.70) in the tranilast group and 6.35 mm (5.50, 7.25) in the control group (p=0.3837). At follow‐up, the diameter of the stricture was 5.60 mm (4.25, 11.23) in the tranilast group and 5.05 mm (4.30, 7.10) in the control group (p=0.1769). Change in diameter during the follow‐up period was 0.48% per month (–0.63, 3.18) in the tranilast group, compared with –0.86% per month (–2.11, 0.88) in the control group (p=0.2740).
We found a preventive effect of tranilast on the development of symptomatic intestinal stricture in patients with Crohn's disease. Since there is no established effective medical therapy for intestinal stricture in Crohn's disease, long‐term tranilast administration has potential as a therapeutic modality for the prevention of the development of intestinal stricture in patients with Crohn's disease.
Competing interests: None declared.
This study was approved by the ethical committee of Osaka City University and informed consent was obtained from all the patients.