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OP021. Steroid-free remission in adalimumab-treated paediatric patients with moderately to severely active Crohn's disease in the IMAgINE 1 trial

A. Griffiths1, W. Crandall2, R. Colletti3, F. Ruemmele4, W.A. Faubion5, J. Hyams6, A. Lazar7, Y. Li8, S. Eichner8, R.B. Thakkar8, 1The Hospital for Sick Children, Department of Paediatrics, Toronto, ON, Canada, 2Nationwide Children's Hospital, Department of Gastroenterology/Nutrition, Columbus, United States, 3University of Vermont, Department of Pediatrics, Burlington, United States, 4Universite Sorbonne Paris-Cite, Hospital Necker-Enfants Malades, APHP, Paris, France, 5Mayo Clinic, Gastroenterology, Rochester, United States, 6Connecticut Children's Medical Center, Division of Digestive Diseases, Hartford, United States, 7AbbVie Deutschland GmbH & Co, KG, GPRD, Ludwigshafen, Germany, 8AbbVie Inc, GPRD, North Chicago, United States

Background

The efficacy of adalimumab (ADA) in inducing and maintaining remission in paediatric patients with Crohn's disease (CD) was demonstrated in IMAgINE 1 [1] (NCT00409682). This analysis further investigated corticosteroid (CS)-free remission in the subset of patients receiving CS at baseline (BL).

Methods

Patients aged 6–17 y with CD resistant or intolerant to conventional therapy, including infliximab (IFX), and BL Paediatric CD Activity Index (PCDAI) >30 received open-label (OL) induction of ADA at weeks (wks) 0/2 by body weight (<40 kg, 80/40 mg; ≥40 kg, 160/80 mg). At wk 4, patients were stratified by response and prior IFX use, and randomized to double-blind (DB) higher-dose (HD) ADA (<40 kg, 20 mg every other wk [eow]; ≥40 kg, 40 mg eow) or lower-dose (LD) ADA (<40 kg, 10 mg eow; ≥40 kg, 20 mg eow) for 48 wks. Patients with disease flare or nonresponse could move to DB weekly dosing after wk 12, then to OL weekly HD ADA for continued flare/nonresponse. Proportions of patients receiving LD ADA vs HD ADA achieving CS-free clinical remission (PCDAI ≤10) were compared using a logistic regression model overall, by prior IFX use, and by BL disease severity (PCDAI: <40, ≥40). Nonresponder imputation was used for missing values and patients who moved to weekly dosing.

Results

Of 188 patients randomized to ADA, 38 in the LD ADA group and 33 in the HD ADA group were using CS at BL. Of these, 33.3% receiving HD ADA and 26.3% receiving LD ADA achieved CS-free remission at wk 26 (P = 0.519) [1] (Table). CS-free remission rates at wk 52 were also numerically higher but did not reach statistical significance for patients receiving HD ADA (27.3%) vs LD ADA (18.4%). Greater proportions of IFX-naïve patients achieved CS-free remission at wk 26 (P =  0.004) compared to patients with prior IFX use (Table). At wk 26, 52.9% of IFX-naïve patients receiving HD ADA were in CS-free remission. BL disease severity did not appear to affect CS-free remission rates.

Table. Proportion of patients achieving CS-free clinical remission
LD ADA
N = 38
HD ADA
N = 33
P value*
Week 26
Overall, n (%)10 (26.3)11 (33.3)0.519
Prior IFX, n/N (%)
 IFX-naive8/22 (36.4)9/17 (52.9)0.303
 IFX-experienced2/16 (12.5)2/16 (12.5)1.000
BL disease severity, n/N (%)
 PCDAI <403/13 (23.1)6/13 (46.2)0.223
 PCDAI ≥407/25 (28.0)5/20 (25.0)0.821
Week 52
Overall, n (%)7 (18.4)9 (27.3)0.376
Prior IFX, n/N (%)
 IFX-naive5/22 (22.7)7/17 (41.2)0.221
 IFX-experienced2/16 (12.5)2/16 (12.5)1.000
BL disease severity, n/N (%)
 PCDAI <403/13 (23.1)3/13 (23.1)1.000
 PCDAI ≥404/25 (16.0)6/20 (30.0)0.268
ADA, adalimumab; BL, baseline; CS, corticosteroid; HD, higher dose; IFX, infliximab; LD, lower dose; PCDAI, Paediatric Crohn's Disease Activity Index.
*P value is from a logistic regression model with treatment as the only predictor.

Conclusion

In paediatric patients with moderately to severely active CD who used CS at BL in IMAgINE 1, trends toward higher CS-free remission rates were observed with HD ADA treatment. CS-free remission rates were higher in IFX-naïve patients than in IFX-experienced patients, but were not clearly affected by BL disease severity [1].

1. Hyams J, et al., (2012), Safety and efficacy of adalimumab for moderate to severe Crohn's disease in children. Gastroenterology, 365.