Adalimumab Associated With Clinical Remission Beyond 1 Year in Pediatric Crohn Disease

Boy having a stomachache holding his belly tightly with two hands with red pain coloring around his stomach
Investigators analyzed adalimumab’s long-lasting clinical remission, associations of trough concentration, and linear growth in pediatric patients with Crohn disease.

Clinical remission is durable beyond 1 year in children with Crohn disease (CD) receiving adalimumab therapy, according to a study in the Journal of Pediatric Gastroenterology and Nutrition.

Investigators aimed to compare the effectiveness of monotherapy vs concomitant immunomodulation for preventing secondary loss of responsiveness (LOR) in a real-world setting. Researchers also sought to evaluate the association of adalimumab exposure with clinical and biomarker remission in pediatric patients with CD and to identify variables associated with treatment failure.

Eligible study participants initiated adalimumab for treatment of luminal CD at a children’s hospital in Toronto from January 2007 to June 2018. At weeks 8 to 12, researchers assessed initial response to induction, and, thereafter, followed patients until they discontinued therapy or until they were transferred to adult care at age 18 years.

A total of 213 children and adolescents (65% male) with luminal CD (median age, 14.1 years [IQR, 12.5-15.7 years]) were included in the study. The median follow-up while receiving adalimumab was 24.3 (IQR, 13.2-37.3) months.

Of the cohort, 86% received standard adult adalimumab induction with 160 mg/80 mg. Adalimumab maintenance was initiated as monotherapy in 79% of participants, including 85% of anti-tumor necrosis factor (TNF)-naive patients and 60% of those with previous infliximab failure.

Steroid-free clinical remission was achieved in 82% of patients, partial response in 13% of patients, and primary nonresponse in 5% of patients. Steroid-free clinical remission occurred more frequently in patients naive to anti-TNF vs those with previous exposure to infliximab (86% vs 70%, P =.008).

Anti-TNF-naive status and inflammatory behavior (odds ratio [OR], 2.39; 95% CI, 1.07-5.31; P =.033 and OR, 3.13; 95% CI, 1.27-7.69; P =.013, respectively) were significantly associated with an increased likelihood of steroid-free clinical remission in the multivariable analysis.

A total of 79% of patients who achieved steroid-free clinical remission were continuing adalimumab at transfer to adult care or last follow-up. Their median follow-up under pediatric care was 24.8 (IQR, 15.6-38.4) months on adalimumab. The 21% of initial remitters who discontinued treatment did so after a median 22.4 (IQR, 18.2-32.6) months owing to adverse events or secondary LOR.

After initial attainment of steroid-free clinical remission, secondary LOR requiring adalimumab discontinuation occurred in 10% of anti-TNF-naive patients at rates of 0%, 8%, and 15% in the first, second, and third years respectively, and in 31% of patients who had received infliximab at rates of 3%, 22% and 52% in the first, second, and third years respectively (P =.001).

Having a maintenance trough concentration (TC) that was consistently greater than 7.5 mg/mL was associated with an increased likelihood of durable clinical remission (hazard ratio [HR], 17.24; 95% CI, 6.33-45.45; P <.001). Having a consistent TC greater than 10 mg/mL was associated with an increased likelihood of biomarker remission (HR, 6.56; 95% CI, 2.27-10.28; P <.001).

In children with Tanner stages 1 to 2 at adalimumab initiation, mean height z scores were lower than at diagnosis but improved significantly during adalimumab therapy.

Among several study limitations, repeat endoscopic and magnetic resonance examinations were not performed for all clinical remitters and were not scored prospectively with validated multi-item measures. Also, the absence of access to a drug-tolerant assay significantly limited the understanding of the antiadalimumab  antibody development rate.

“Clinical remission was very durable in our cohort, with nearly 80% of the previously anti-TNF-naive cohort remaining on therapy during follow-up throughout pediatric care,” the researchers wrote. “Importantly, [adalimumab] response was durable even given as monotherapy.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Rinawi F, Popalis C, Tersigni C, et al. Long-term outcomes with adalimumab therapy in pediatric Crohn disease: associations with adalimumab exposure. J Pediatr Gastroenterol Nutr. 2022;74(3):389-395. doi:10.1097/MPG.0000000000003366