Development of a data bank for officer effectiveness ratings. Project 7717, Task 17110, Contract AF 41 (657)-244, Data Processing Center.

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Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial.

Background Biomarkers of intestinal inflammation, faecal calprotectin (FC) and C-reactive protein (CRP), have been recommended to monitor patients with Crohn’s disease (CD), but whether their use in treatment decisions improves outcomes remains unknown. In CALM, we compared endoscopic and clinical outcomes at 48 weeks in moderate to severe CD managed with a tight control (TC) algorithm utilising clinical symptoms and biomarkers versus clinical management (CM) algorithm. Methods CALM (ClinicalTrial.gov number NCT01235689) was an open-label, multicentre, Phase 3 study in adult patients naïve to immunomodulator and biologics with active endoscopic CD (CD Endoscopic Index of Severity (CDEIS)&gt;6 and sum of CDEIS subscores &gt;6 in ≥1 segment with ulcers ). Patients were randomised 1:1 to TC or CM groups after 8 weeks of prednisone induction therapy or earlier if they had active disease. In both groups, treatment was escalated in a step-wise manner from no treatment to adalimumab induction+every other week, every week (EW), and EW+azathioprine based on meeting failure criteria (FC≥250 g/g, CRP≥5mg/L, Crohn’s Disease Activity Index [CDAI]≥150, and/or prednisone for TC and CDAI and/or prednisone for CM). De-escalation was possible for adalimumab EW±azathioprine if failure criteria were not met. The primary endpoint of mucosal healing (CDEIS&lt;4) with absence of deep ulcers was assessed 48 weeks post-randomisation. Findings A total of 244 patients (mean disease duration approximately 1 year) were randomised. Significantly higher proportion of patients in TC achieved the primary endpoint at week 48 (45·9%, n56) than in CM (30·3%, n37) with CMH adjusted risk difference of 16·1% (95% CI 3·9–28·3), p0·010). The overall rate of adverse events was similar between TC and CM. Interpretation Monitoring therapy using symptoms and biomarkers of inflammation led to superior endoscopic and clinical outcomes in CD after 48 weeks post-randomisation compared with symptom-driven decisions alone.</p

Endoscopic and deep remission at 1 year prevents disease progression in early Crohn’s disease: long-term data from CALM

Background We aimed to describe the long-term impact of achieving endoscopic and deep remission among participants in the effect of tight control management on CD (CALM) trial. Methods We analysed medical records from patients with follow-up data since end of CALM. Patients were stratified by outcomes in CALM at 1 year: clinical remission (Crohn’s disease activity index, CDAI &lt;150), endoscopic remission (Crohn’s disease endoscopic index of severity, CDEIS &lt;4 with no deep ulcerations), and deep remission (CDAI &lt;150, CDEIS &lt;4 with no deep ulcerations, and no steroids for ≥8 weeks). The primary outcome was a composite of major adverse outcomes reflecting CD progression: new internal fistula/abscess, stricture, perianal fistula/abscess, CD hospitalisation, or CD surgery since end of CALM. Kaplan–Meier and Cox regression methods were used to compare composite rates between patients who achieved or did not achieve remission at 1 year. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) are reported, controlling for randomisation arm and baseline variables significant at p &lt; 0.2 level. Results One hundred twenty-two patients with median age 29 years (IQR 22.5–37) and median disease duration 0.2 years (IQR 0.1–0.8) were included. Median follow-up time from end of CALM was 3.02 years (range 0.05–6.26 years). Fifty per cent were randomised to the tight control arm. There were no significant differences in baseline characteristics in patients with follow-up data and those lost to follow-up with the exception of a slightly higher CDEIS score in patients lost to follow-up (14.6 vs. 12.9, p = 0.04). Thirty-four patients (27.9%) had a major adverse outcome during follow-up. Patients in clinical remission at 1 year did not have significantly lower rates of the composite endpoint (log-rank p = 0.15). Patients in endoscopic and deep remission at the end of CALM were significantly less likely to have a major adverse event over time (Figures 1 and 2). After adjusting for age, disease duration, prior surgery, prior stricture, and randomisation arm, endoscopic remission (aHR 0.44, 95% CI 0.20–0.96, p = 0.038) and deep remission (aHR 0.25, 95% CI 0.09–0.72, p = 0.01) were significantly associated with lower risk of major adverse events. Conclusions Early CD patients who achieve endoscopic or deep remission after 1 year of intensive treatment are less likely to have disease progression over a median of 3 years.</p