Improvement in Markers of Bone Metabolism with Adalimumab in Children with Moderately to Severely Active Crohnʼs Disease: Results from IMAgINE 1

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Purpose: To measure changes in bone metabolism in pediatric patients (pts) with moderately to severely active Crohn's disease (CD) treated with adalimumab (ADA) enrolled in the clinical trial IMAgINE 1. Methods: In IMAgINE 1,1 pts aged 6-17 years with baseline (BL) PCDAI >30 and CD resistant or intolerant to conventional therapy, including prior infliximab, received open-label induction of ADA at wks 0/2 according to body weight (≥40 kg, 160/80 mg; <40kg, 80/40 mg). At wk 4, pts were randomized to double-blind higher-dose (HD) ADA (≥40 kg, 40 mg every other week [eow]; <40 kg, 20 mg eow) or lower-dose (LD) ADA (≥40 kg, 20 mg eow; <40 kg, 10 mg eow). Pts experiencing disease flare or non-response could move to blinded weekly dosing after wk 12. Changes in serological markers of bone formation (osteocalcin [OC], bone specific alkaline phosphatase [BSAP]) and resorption (serum type I collagen N-telopeptide [NTx]) from BL were calculated at wk 26 and 52 for LD and HD ADA. Subgroup analyses by prior IFX use, disease severity at BL, and response at wk 4 (defined as PCDAI decrease ≥15 points from BL) were also performed. Last observation carried forward (LOCF) was used to impute missing data. Signed rank test was applied to evaluate changes within each treatment group. Results: Overall, pts achieved improvement in OC and BSAP with LD and HD ADA at wks 26 and 52 (Table). Increases in OC and BSAP were achieved with both doses at wks 26 and 52 in pts naïve to prior IFX and with severe disease (PCDAI ≥40). BSAP improvement was more pronounced in wk 4 responders. Significant change in NTx was observed at wk 26 with HD ADA (Table).Table: Table. Median BL values of serological markers of bone metabolism and median change from BL at wks 26 and 52 (LOCF)Conclusion: Both HD and LD ADA treatment improved bone metabolism in children with moderately to severely active CD. Pts naïve to IFX derived the greatest treatment benefit.