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

Journal article

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)>6 and sum of CDEIS subscores >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<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%, n56) than in CM (30·3%, n37) with CMH adjusted risk difference of 16·1% (95% CI 3·9–28·3), p0·010). 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.

Authors: Colombel, J; Panaccione, R; Bossuyt, P; Lukas, M; Baert, F

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Lancet
• Volume: 390
• Issue: 10114
• Pages: 2779-2789
• Publication date: 2017-10-31
• Acceptance date: 2017-09-15
• DOI: 10.1016/s0140-6736(17)32641-7
• EISSN: 1474-547X
• ISSN: 0140-6736
• Pmid: 29096949
• Language: English
• Keywords: Journal Article