P-097: Impact of concomitant immunosuppressant use on adalimumab efficacy in children with moderately to severely active Crohn’s disease: results from IMAgINE 1

Abstract

Background The impact of non-biologic immunosuppressants (IMMs) concomitantly administered with adalimumab (ADA) was evaluated in pediatric patients (pts) with moderately to severely active Crohn's disease (CD) in the randomized clinical trial IMAgINE 1 (NCT00409682). Methods In IMAgINE 1,1 pts aged 6-17 years with baseline Pediatric 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 randomized 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. 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. Gastroenterology. 2012;143:365-374. Proportion of Patients by IMM Use at Baseline Achieving Clinical Remission (PCDAI ≤10) at Week 26