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P458. Impact of concomitant immunosuppressant use on adalimumab efficacy in children with moderately to severely active Crohn's disease: Results from IMAgINE 1

J. Hyams1, F. Ruemmele2, R. Colletti3, J. Kierkus4, J. Rosh5, S. Eichner6, A. Lazar7, Y. Li6, R.B. Thakkar6, 1Connecticut Children's Medical Center, Division of Digestive Diseases, Hartford, United States, 2Universite Sorbonne Paris-Cite, Hospital Necker-Enfants Malades, APHP, Paris, France, 3University of Vermont, Department of Pediatrics, Burlington, United States, 4The Children's Memorial Health Institute, Gastroenterology, Hepatology and Feeding Disorders, Warsaw, Poland, 5Goryeb Children's Hospital/Atlantic Health, Pediatric Gastroenterology, Morristown, United States, 6AbbVie Inc, GPRD, North Chicago, United States, 7AbbVie Deutschland GmbH & Co, KG, GPRD, Ludwigshafen, Germany

Background

The impact of non-biologic immunosuppressants (IMMs) concomitantly administered with adalimumab (ADA) was evaluated in paediatric patients (pts) with moderately to severely active Crohn's disease (CD) in the randomised clinical trial IMAgINE 1 (NCT00409682).

Methods

In IMAgINE 1 [1], pts aged 6–17 years with baseline Paediatric Crohn's Disease Activity Index (PCDAI) scores >30 and CD resistant or intolerant to conventional therapy, including prior infliximab, received open-label induction of ADA at weeks (wks) 0/2 according to body weight (≥40 kg, 160/80 mg; <40 kg, 80/40 mg). At wk 4, pts were randomised to double-blind higher-dose (HD) ADA (≥40 kg, 40 mg every other wk [eow]; <40 kg, 20 mg eow) or lower-dose (LD) ADA (≥40 kg, 20 mg eow; <40 kg, 10 mg eow). In pts meeting clinical response criteria, IMMs could be discontinued at or after wk 26. The proportion of pts receiving concomitant IMMs achieving clinical remission (PCDAI ≥10) at wk 26, and the proportion who discontinued IMMs and were in clinical remission or achieved clinical response (decrease in PCDAI of ≥15 from baseline) at wk 52 were evaluated. Non-responder imputation (NRI) was used for wk 26 outcomes when data were missing or pts had escalated dosing. In addition, modified NRI (mNRI) was used for wk 26 and 52 analyses, which considered pts as responders or non-responders after blinded dose escalation. Adverse events (AEs) in subpopulations by concomitant IMM were assessed.

Results

At baseline, 57 pts (60%) in the LD ADA group and 60 (64.5%) in the HD ADA group reported IMM use. At wk 26, clinical remission was achieved by 42/117 (35.9%) and 21/71 (29.6%) of ADA-treated pts with or without baseline IMMs, respectively (table). Of the pts who achieved clinical remission at wk 26 (mNRI) and discontinued IMMs, 5/21 (23.8%) in the LD group and 6/27 (22.2%) in the HD group maintained clinical remission at wk 52. Of the pts who achieved clinical response at wk 26 (mNRI), 9/36 (25.0%) and 13/44 (29.5%), respectively, maintained clinical response at wk 52. The proportion of pts experiencing serious infectious AEs was similar in pts with (5.8%) or without (7.0%) concomitant IMMs. Of pts who developed anti-ADA antibodies (HD, n = 4; LD, n = 2), 1 in each dose group was on IMMs.

Table: Proportion of patients by IMM use at baseline achieving clinical remission (PCDAI ≤10) at Week 26
IMM use at baselineADA lower-dose
20 mg/10 mg eow, n/N (%)
ADA higher-dose
40 mg/20 mg eow, n/N (%)
Overall, n/N (%)
No11/38 (28.9)10/33 (30.3)21/71 (29.6)
 No IMM or steroid6/20 (30.0)3/15 (20.0)9/35 (25.7)
Yes16/57 (28.1)26/60 (43.3)42/117 (35.9)
 IMM, no steroid10/37 (27.0)22/45 (48.9)32/82 (39.0)
 IMM + steroid6/20 (30.0)4/15 (26.7)10/35 (28.6)
ADA, adalimumab; eow, every other week; IMM, immunosuppressant; PCDAI, Paediatric Crohn's Disease Activity Index.

Conclusion

In children with moderate to severe CD treated with ADA, the rates of clinical remission with and without concomitant IMM use were not different. Concomitant IMMs did not affect the incidence of serious infections.

1. Hyams JS, et al. (2012), Safety and efficacy of adalimumab for moderate to severe Crohn's disease in children. Gastroenterology, 365–374.