Tu1944 Efficacy and Safety of Standard vs Low Dose Adalimumab Maintenance Therapy As a Function of Disease Severity in Pediatric Patients With Crohn's Disease: Subanalysis of Imagine 1

Abstract

Aim: Adalimumab (ADA) has been shown to be an effective treatment for inducing and maintaining clinical remission and/or response in children with moderate to severe Crohn's disease (CD)1. Although the standard adult dose (SD) ADA maintenance therapy exhibited generally greater efficacy than low dose (LD)1, the influence of baseline (BL) disease severity on outcomes has not been determined. Methods: In IMAgINE11, patients (pts) aged 6-17 years that had a PCDAI score .30 at BL, with CD resistant or intolerant to conventional therapy, including prior infliximab (IFX), received open-label induction ADA at weeks (wks) 0/2 according to bodyweight (≥40kg, 160/80mg;,40kg, 80/40mg). At wk4, 188 randomized pts (ITT population) received either double-blind SD ( ≥40kg, 40mg every other wk (eow); ,40kg, 20mg eow) or LD (≥40kg, 20mg eow; ,40kg, 10mg eow) maintenance therapy. After wk12, pts could move to blinded weekly (ew) dosing for disease flare or non-response. Clinical remission (PCDAI≤10) and response (PCDAI decrease ≥15 points from BL) were measured at wk52. Subgroup analyses by disease severity, based on the median BL PCDAI observed for the study population (less severe CD, PCDAI,40; more severe CD, PCDAI≥40), and also by prior IFX use were performed. Non-responder imputation was used for missing data or after switch to ew therapy. Treatment-emergent adverse events (AE) were reported as events/100pt-years (E/100PY) for any pt receiving at least one dose of ADA. Results: Greater clinical remission and response was achieved with SD ADA therapy compared to LD at wk52 in pts with more severe disease, with the greatest difference between doses occurring in IFX Naive pts. For pts with less severe CD, similar rates of remission and response were observed between SD and LD ADA (Table). Switch to ew dosing occurred most frequently in pts with more severe CD receiving LD ADA (55.6%) than in pts with less severe CD receiving the same dose (43.9%). For pts receiving SD ADA, escalation to ew dosing occurred in a similar percentage of pts, regardless of BL disease severity (35.9%, less severe; 38.9%, more severe). The overall rate of AEs was similar between dosing groups for either pt population. For pts with less severe CD, serious AEs (SAEs) were higher with SD (32.0 E/100PY) than LD ADA (17.6 E/100PY), whereas a similar rate of SAEs was observed between SD and LD ADA in pts with more severe disease (54.8 vs 64.5 E/ 100PY, respectively). No malignancies, TB, congestive heart failure or deaths were reported. Conclusion: At wk52, SD maintenance ADA was a more effective therapy than LD for children with more severe CD, whereas pts with less severe disease benefitted equally from both doses. The greatest remission and response rates were observed for IFX-Naive pts. The overall safety profile was similar for SD and LD ADA treatment. 1.Hyams 2012 Gastroenterology;143:365 Clinical outcomes in pediatric CD pts with eow SD vs eow LD ADA (ITT population)