Children with Crohn’s disease often have impaired growth. The IMAgINE 1 trial demonstrated the safety and effectiveness of Adalimumab ( Humira ) on inducing and maintaining remission in children with moderately to severely active Crohn’s disease.
The impact of Adalimumab therapy on growth in patients with delayed growth at trial entry is analyzed.
In IMAgINE 1, patients aged 6-17 years with baseline PCDAI more than 30 received open-label induction of Adalimumab at weeks 0/2 according to body weight ( greater than or equal to 40kg, 160/80mg; less than 40kg, 80/40mg ).
At week 4, patients were randomized to double-blind higher-dose Adalimumab ( greater than or equal to 40kg, 40mg every other week [ EOW ]; less than 40kg, 20mg EOW ) or lower-dose Adalimumab ( greater than or equal to 40kg, 20mg EOW; less than 40kg, 10mg EOW ) to week 52.
Patients were allowed to escalate to blinded weekly therapy for flare or non-response, followed by open-label higher-dose Adalimumab weekly for continued flare or non-response.
Change from baseline in height velocity z-score was measured at weeks 26 and 52 in patients with and without growth delay at baseline ( defined as height velocity z-score less than or equal to -1.0 ) in all Adalimumab patients regardless of treatment group.
Subgroup analyses by baseline corticosteroid use, disease severity based on median baseline PCDAI of study population ( PCDAI less than 40, moderate Crohn’s disease; PCDAI greater than or equal to 40, severe Crohn’s disease ), and prior Infliximab ( Remicade ) use were performed.
Overall, statistically significant improvement in growth was observed at weeks 26 and 52 with Adalimumab maintenance therapy in patients with growth delay ( median height velocity z-score at baseline -2.9 and median change from baseline at weeks 26 and 52; 2.4 and 3.3, respectively, each p less than 0.001 ), but not in patients with normal growth ( baseline median 0.2; median change from baseline=0 at weeks 26 and 52 ).
No statistically significant differences between lower-dose and higher-dose Adalimumab were observed.
Growth improvement trended to be larger in patients with baseline corticosteroid use, with severe Crohn’s disease, and in Infliximab naïve patients.
In conclusion, Adalimumab treatment significantly improved growth in children with moderately to severely active Crohn’s disease and growth delay.
The pronounced effect of Adalimumab on growth in children with concomitant corticosteroid use or severe disease by PCDAI requires confirmatory studies. ( Xagena )
Source: UEG ( United European Gastroenterology ) Week, 2014