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16. Relationships between clinical remission, C-reactive protein normalization and mucosal healing in Crohn's disease: analyses from the SONIC trial

L. Peyrin-Biroulet1, W. Reinisch2, J.-F. Colombel3, G.J. Mantzaris4, A. Kornbluth5, R. Diamond6, P. Rutgeerts7, K.L. Tang6, F.J. Cornillie8, W. Sandborn9, 1University Hospital of Nancy-Brabois, France, 2Universitätsklinik für Innere Medizin IV, Austria, 3Hôpital Claude Huriez, France, 3Evangelismos Hospital, Greece, 5Mount Sinai Medical Center, United States, 6Janssen Biotech, Inc, United States, 7University Hospital, Gasthuisberg, Belgium, 8Janssen Biotechnology BV, Netherlands, 9University of California San Diego, United States

Background

The CDAI has been criticized due to heavy weighting on subjective clinical symptoms, such as abdominal pain and decreased sense of well-being. Biomarker CRP and endoscopic lesions are objective measures of inflammation. We investigated the relationships between clinical remission, CRP normalization, & mucosal healing (MH) in CD in SONIC.

Methods

SONIC was a randomized, controlled trial comparing infliximab (IFX) to azathioprine (AZA) and to IFX plus AZA for the treatment of 508 CD-pts naïve to immunomodulators & biologics. CD activity, measured by CDAI, CRP, and ileocolonoscopy was evaluated at baseline (BL) and at wk26. Mucosal healing was defined as absence of mucosal ulceration at wk26 ileocolonoscopy in a pt who had evidence of ulceration present at BL ileocolonoscopy.

Results

188 pts who had evidence of mucosal ulceration at BL, evaluable ileocolonoscopy, CDAI scores and CRP values at BL and at wk26 were included in this analysis. 140/188 pts (74.5%) had BL elevated CRP (CRP ≥0.5 mg/dL). Seventy-two of 136 pts (52.9%) who were in clinical remission (CDAI <150) at wk26 achieved MH, while 54 (39.7%) achieved both CRP normalization (CRP <0.5 mg/dL) and MH. Sensitivity and specificity of CDAI remission and CDAI moderate-to-severe disease activity to predict MH and CRP normalization in CD are provided (Table). PPV and NPV of CDAI to detect MH using 150 as a cutoff for CDAI were 65.4% & 52.9%, & 80.8% & 39.7% to detect MH and/or CRP normalization, resp. Among the 27 pts (14.4%) who had persistent moderate-to-severe disease (CDAI ≥220) at wk26, 8 (29.6%) achieved MH and 6 (22.2%) achieved CRP normalization & MH. PPV & NPV of CDAI to detect MH using 220 as a cutoff for CDAI were 70.4% & 50.9%, & 77.8% & 36% to detect MH and/or biomarker remission, resp.

Table: Sensitivity and specificity of CDAI remission and CDAI moderate-to-severe disease activity to predict MH & CRP normalization in CD
 CDAI < 150 (N = 136)
CDAI ≥ 150 (N = 52)
CDAI ≥ 220 (N = 27)
CDAI < 220 (N = 161)
Complete MH72/136 (52.9%)8/27 (29.6%)
 Sensitivity/Specificity (%)80.0/34.791.1/19.4
CRP normalization (<0.5 mg/dL)88/136 (64.7%)13/27 (48.2%)
 Sensitivity/Specificity (%)81.5/4088.0/17.5
CRP normalization & MH54/136 (39.7%)6/27 (22.9%)
 Sensitivity/Specificity (%)84.4/33.990.6/16.9

Conclusion

Half of CD pts in clinical remission have endoscopic and/or CRP evidence of residual active CD, whereas other pts with endoscopic and CRP normalization have persistent clinical symptoms. These findings demonstrate that CD clinical symptoms scored by CDAI are not a reliable measure of underlying inflammation. Objective outcome measures of CD activity beyond clinical symptoms need to be further evaluated.