Highlights from

ECCO 2019

European Crohn's and Colitis Organisation's 14th congress

Copenhagen 6-9 March 2019

Proactive adalimumab trough measurements increase corticosteroid-free clinical remission

In biological-naïve children with luminal Crohn’s disease (CD) who responded to adalimumab induction, repeated proactive trough measurements plus tight control resulted in higher corticosteroid-free sustained remission rates than reactive trough measurements and tight control.

This was the first paediatric randomised controlled trial to determine whether proactive therapeutic drug monitoring to maintain serum levels of adalimumab above 5 μg/mL is associated with higher rates of clinical remission than the reactive approach, based on drug measurement only when clinically indicated. First author Dr A. Assa (Schneider Children’s Hospital, Israel) received the ECCO 2019 award for best researcher-initiated study for this abstract.

He explained that 80 children between 6–18 years of age with luminal CD who responded to adalimumab induction (week 4) were randomly assigned into proactive and reactive groups. In the proactive group, trough concentrations were measured at week 4, 8, and every 8 weeks thereafter until week 72; dose (when lower than 40 mg) or intervals were adjusted in-order to maintain levels higher than 5 μg/mL. In the reactive group, physicians were informed of the trough levels only when clinically indicated, adjusting dose/intervals based upon the levels.

The primary endpoint was sustained corticosteroid-free clinical remission from week 8 to 72, defined as Paediatric Crohn’s Disease Activity Index (PCDAI) <10, using non-responder imputation. This endpoint was met by significantly more children in the proactive group: 34 (87%) vs 21 (49%) in the reactive group (P<0.001). At week 72, corticosteroid-free clinical remission on adalimumab was reached by 32 (82%) and 20 (48%) in the proactive and reactive group; respectively (P<0.001). Clinical indices, C-reactive protein, and faecal calprotectin correlated with adalimumab trough concentrations. Faecal calprotectin reduction rate was significantly higher in the proactive group. There were more patients undergoing dose/interval adjustments in the proactive group: 32 (82%) vs 18 (44%) (P<0.001).

Dr Assa concluded that children with CD treated with adalimumab may benefit from therapeutic drug monitoring, even though severe exacerbations and drug discontinuation rates were similar. He added: “Since adalimumab intensification is the rule rather than the exception, this calls for early optimisation of trough concentrations.”

Assa A, et al. Proactive adalimumab trough measurements increase corticosteroid-free clinical remission in paediatric patients with Crohn’s disease: the paediatric Crohn’s disease adalimumab-level-based optimisation treatment (PAILOT) trial. ECCO 2019, OP18.

Top image: © Pornpak Khunatorn

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