Randomised clinical trial: deep remission in biologic and immunomodulator naïve patients with Crohn's disease - a SONIC post hoc analysis.

Abstract

BACKGROUND:

As treatment goals in Crohn's disease (CD) evolve, targets now include clinical remission (CR), mucosal healing (MH) and biological remission [C-reactive protein normalisation (CRPnorm )].

AIMS:

To evaluate the association of baseline factors and treatment with the achievement of different composite remission parameters at week 26.

METHODS:

This post hoc analysis of the SONIC trial evaluated different composite remission measures at week 26 in a subgroup of patients with Crohn's disease activity index (CDAI) scores, CRP, and endoscopic data available at baseline and week 26 (N = 188). Assessed composite remission measures were: CR (CDAI < 150) and MH (absence of any mucosal ulcerations), previously referred to as 'deep remission;' and alternative composite endpoints: CR + CRPnorm (CRP < 0.8 mg/dL); CRPnorm  + MH; and CR + CRPnorm  + MH.

RESULTS:

Among analysed patients, 136/188 (72.3%) achieved CR and 90/188 (47.9%) achieved MH at week 26. All composite outcomes were significantly greater (Bonferroni significance level, P ≤ 0.016) with combination therapy (i.e. infliximab and azathioprine; 52.3-63.6%) vs. azathioprine monotherapy (12.9-29.0%; p ≤ 0.005 for all comparisons). Composite remission rates including MH were significantly greater with combination therapy (52.3-56.9%) vs. infliximab (25.6-32.3%; P ≤ 0.015 for all comparisons except CRPnorm  + MH, P = 0.017) and vs. azathioprine monotherapy (12.9-20.4%; P ≤ 0.002 for all comparisons). Median serum trough infliximab concentrations among patients who achieved MH or CR + MH were greater when compared with those among patients who did not achieve MH (P = 0.018) or CR + MH (P = 0.053). Among the subgroup of patients with early Crohn's disease, MH alone or in combination with composite remission criteria significantly improved clinical outcomes of patients who received combination therapy.

CONCLUSIONS:

Combination therapy was more effective in achieving various composite remission measures vs. azathioprine or infliximab monotherapy. These data illustrate that 'deep remission' is achievable with combination therapy in a high percentage of patients with early Crohn's disease. ClinicalTrials.gov number: NCT00094458.

• Authors: J-F Colombel, W Reinisch, G J Mantzaris, A Kornbluth, P Rutgeerts, K L Tang, A Oortwijn, G S Bevelander, F J Cornillie, W J Sandborn
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 41 Issue 8 Pg. 734-46 (Apr 2015) ISSN: 1365-2036 [Electronic] England
• PMID: 25728587 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 John Wiley & Sons Ltd.

Chemical References

• Antibodies, Monoclonal
• Gastrointestinal Agents
• Immunosuppressive Agents
• C-Reactive Protein
• Infliximab
• Azathioprine

Topics

• Adult
• Antibodies, Monoclonal (administration & dosage, therapeutic use)
• Azathioprine (administration & dosage, therapeutic use)
• C-Reactive Protein (metabolism)
• Crohn Disease (drug therapy)
• Drug Therapy, Combination
• Endoscopy, Gastrointestinal
• Female
• Gastrointestinal Agents (administration & dosage, therapeutic use)
• Humans
• Immunosuppressive Agents (administration & dosage, therapeutic use)
• Infliximab
• Intestinal Mucosa (metabolism)
• Male
• Patient Acuity
• Quality of Life
• Remission Induction