P502 Clinical and endoscopic features of secondary loss of response cases in patients with Crohn’s disease treated with infliximab by top-down strategy: A case–control study

Abstract

Background: Top-down strategy of treatment with anti-TNF agents improve possible therapeutic efficacy or prognosis in patients with Crohn's disease (CD), especially high-risk CD patients. However, there are few reports on the evaluation of clinical and endoscopic features of secondary loss of response (LOR) CD cases after treatment with infliximab (IFX) by top-down strategy. Method(s): Among 410 CD patients treated with IFX between December 2004 and May 2010 in our hospital, top-down IFX treatment cases were identified with less than 2 years of disease duration, no treatment history of steroid/immunomodulator/biologics, and no history of surgery. IFX treatment was considered effective when Crohn's disease activity index (CDAI) decreased by >70 points; endoscopy was considered effective when the simple endoscopic score for CD (SES-CD) decreased by >50%. LOR was identified by an increase of >50 points in CDAI or the need for additional treatment. Result(s): We retrospectively investigated 58 CD cases with top-down IFX treatment. Cumulative remission rates were 83.3, 68.6, and 57.6% after 1, 2, and 5 years, respectively. Patients with <0.6 mg/dl of baseline C-reactive protein (CRP) exhibited significantly higher cumulative remission rates than those with CRP levels of >0.6 mg/dl. LOR cases (n = 24, 8.5 +/- 1.78 months) represented significantly (p = 0.03) longer disease durations than non-LOR cases (n = 34, 4.0 +/- 1.7 months). Other factors, including concomitant immunomodulator treatment, did not differ between the two groups. Additionally, disease durations of primary non-responders (17.0 +/- 1.8 months) were significantly (p = 0.02) longer than those of other cases (5.0 +/- 1.7 months). SES-CD values in the LOR and non-LOR groups were 33.3 and 75.0%, respectively at Week 26, and 50.0 and 83.3%, respectively at Week 52. Among SES-CD at Week 52, the amounts of improvement of left colon score in the LOR group (0.25 +/- 2.18) were significantly (p < 0.01) lower than those in the non-LOR group (3.82 +/- 2.30); however, those of right colon score in the LOR group (2.36 +/- 2.06) was not different (p = 0.83) to those in the non-LOR group (3.52 +/- 2.64). Similarly, rectum score was higher in the LOR group than those in the non-LOR group; however, scores for other segments decreased in both groups. Longitudinal ulcers or cobble stone appearances in the left colon in the LOR group tended to not improve compared with those in the non-LOR group. Conclusion(s): Despite top-down IFX administration, LOR could occurred. Longer disease durations, and longitudinal ulcers or cobblestone appearances in the left colon are possibly associated with LOR.