Proactive adalimumab trough measurements

In biological-naïve children with luminal Crohn’s disease 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.

These were the main outcomes of the first-ever 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, in which drug measurement is only done when clinically indicated [1]. First author Dr Amit Assa (Schneider Children’s Hospital, Israel) received the ECCO 2019 award for best researcher-initiated study for this abstract.

A total of 80 children aged 6-18 years who responded to adalimumab induction were randomised to a proactive or a reactive group. In the proactive group, trough concentrations were measured at week 4, 8, and every 8 weeks thereafter until week 72. Dose or intervals were adjusted to maintain levels >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. Significantly more children in the proactive group met this endpoint: 34 (87%) vs 21 (49%) (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 Crohn’s disease 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.”

1. Assa A, et al. ECCO 2019, OP18.



Posted on 9 May, 20199 April, 2024