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P403 Combined therapy with anti-TNF and immunomodulator is superior to monotherapy for postoperative prophylaxis in Crohn’s disease after intestinal resection: a retrospective analysis from a tertiary centre

A. O’Connor*1, J. Taylor1, N. Scott2, C. Selinger1, J. Hamlin1, A. Ford1, 3

1Leeds Gastroenterology Institute, Leeds, United Kingdom, 2St James’s University Hospital, Histopathology, Leeds, United Kingdom, 3University of Leeds, Leeds Institute of Biochemical and Clinical Sciences, Leeds, United Kingdom

Background

Without treatment, postoperative recurrence rate for patients having intestinal resections for Crohn’s disease (CD) is 70%–90% within a year and 83%–100% within 3 years. Prophylactic medication has been proposed to decrease clinical and endoscopic recurrence. Clinical guidelines are heterogeneous, and many practitioners adopt a pragmatic approach for patients on a case-by-case basis.

Methods

All patients undergoing intestinal resection for CD from January 1, 2009, to December 31, 2013, were identified from our university hospital database. Endpoint of the study was steroid-free, resection-free survival without change or escalation of therapy at end of follow-up. Clinical information was extracted from chart review, endoscopy and radiology reports and prescription data.

Results

In total, 152 patients were analysed. The most common surgery was ileocaecal resection (67.8%). Further, 31.6% (n = 48) of surgeries were emergency procedures. In addition, 69.7% (n = 106) patients had immunomodulatory therapy between surgery and the end of follow-up. Median follow-up was 32 months. Outcomes are outlined in Table 1 and 2.

Table 1. Outcomes of first-line therapy after surgery

Table 2. Likelihood of reaching endpoint for treatment modalities with p-values

Thiopurines were used as first-line monotherapy for 77 patients. Endpoint was reached in 40% with median follow-up of 25 months. Intolerance was observed in 23%. Eight received mercaptopurine as second-line monotherapy, all of whom had failed to tolerate azathioprine as first-line monotherapy. Moreover, 75% were intolerant, and 25% achieved endpoint. Eleven received anti-TNF monotherapy as first line. Endpoint was achieved in 45%. Intolerance was observed in 15%. Further, 14 received anti-TNF monotherapy as second-line treatment; 44% achieved endpoint, and 28% were intolerant; 13 received first-line combination therapy with an anti-TNF and immunomodulator; 86%achieved endpoint at end of follow-up; but 2 patients developed new perianal disease. One of them was intolerant of the drug, and 19 had combination therapy as second- or third-line, with 79% reaching endpoint and 1 intolerant of the drug. In total, 46 of 113 monotherapy events led to endpoint being reached compared with 26 of 32 combination therapy events (p-value < 0.0001).

Conclusion

Thiopurine monotherapy was of poor efficacy and poorly tolerated as postoperative prophylaxis in patients with Crohn’s disease. Combination therapy with thiopurine and anti-TNF appears to be well tolerated and durable, with superior efficacy to monotherapy with either agent alone.