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


OBJECTIVE
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.
The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
J-F
JF
Colombel
W
W
Reinisch
G J
GJ
Mantzaris
A
A
Kornbluth
P
P
Rutgeerts
K L
KL
Tang
A
A
Oortwijn
G S
GS
Bevelander
F J
FJ
Cornillie
W J
WJ
Sandborn
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D001379:Azathioprine / Q000008:administration & dosage / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000378:metabolism; D003424:Crohn Disease / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D016099:Endoscopy, Gastrointestinal; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D062072:Patient Acuity; D011788:Quality of Life; D012074:Remission Induction
D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D007166:Immunosuppressive Agents; D002097:C-Reactive Protein; D000069285:Infliximab; D001379:Azathioprine