Adalimumab improves clinical remission in children with ulcerative colitis

Treatment with adalimumab improved clinical remission and response rates in paediatric patients with moderate-to-severe ulcerative colitis, according to the ENVISION I* study.

“On the basis of the available evidence, [tumour necrosis factor (TNF)] inhibitors, such as adalimumab, appear to be well tolerated and efficacious for the treatment of children with moderate-to-severe ulcerative colitis,” said the researchers.

This phase III trial involved 93 children (mean age 14.1 years, 55 percent female) with moderate-to-severe ulcerative colitis. Seventy-seven were randomized to receive double-blind adalimumab (ITT-E cohort: high dose** [n=47] or standard dose** [n=30]) for an 8-week induction period, while 16 received open-label high-dose adalimumab. At week 8, the 74 participants who achieved partial Mayo score (PMS) remission (defined as a decrease in PMS of ≥2 points and ≥30 percent from baseline) continued to receive high-dose*** or standard-dose*** adalimumab (pooled maintenance adalimumab group: n=62, 31 in each group) for a 52-week maintenance period, while the rest were given placebo. [Lancet Gastroenterol Hepatol 2021;6:616-627]

The study design was changed because of enrolment issues due to non-acceptance of placebo and an external adult placebo group from a meta-analysis was then used as a comparator.

In the ITT-E cohort, a significantly higher percentage of patients in the high-dose adalimumab group achieved PMS remission at week 8 compared with the external placebo group (60.0 percent vs 19.8 percent; adjusted p=0.0001).

Although not significant, more standard-dose adalimumab recipients also achieved PMS remission at week 8 than external placebo recipients (43.0 percent vs 19.8 percent; p=0.38).

In the maintenance ITT-E cohort, significantly more patients, who were PMS responders at week 8, in the high-dose adalimumab group achieved full Mayo score (FMS) remission at week 52 than those in the external placebo group (45.0 percent vs 18.4 percent; adjusted p=0.0001).

More patients in the standard-dose adalimumab than the external placebo group also achieved FMS remission at week 52, although this was not significant (29.0 percent vs 18.4 percent; p=0.38).

Overall, the pooled induction and maintenance adalimumab groups showed significantly better clinical remission rates at week 8 (PMS: 53.0 percent vs 19.8 percent; adjusted p<0.0001) and week 52 (FMS: 37.0 percent vs 18.4 percent; adjusted p=0.0001), respectively, than the external placebo group.

Treatment-emergent adverse events rates were 56.0 percent and 67.0 percent during the adalimumab induction and maintenance periods, respectively, with only 3 percent leading to discontinuation in each treatment period.

No cases of malignancies, tuberculosis, demyelinating diseases, or deaths were reported. “The safety profile was consistent with that of previous adalimumab studies in adults with ulcerative colitis, paediatric patients with Crohn’s disease, and other indications,” noted the researchers.

In conclusion, treatment with adalimumab through week 52 continued to show clinically meaningful rates of clinical remission, including steroid-free remission and mucosal healing, in this paediatric population with moderate-to-severe ulcerative colitis, said the researchers.

“No new safety signals were observed, suggesting that adalimumab is an efficacious and safe treatment option for children with moderate-to-severe ulcerative colitis,” they added.

“To date, ENVISION I is the largest phase III study of a biologic therapy in paediatric patients with moderate-to-severe ulcerative colitis … [and] to our knowledge, adalimumab is the first subcutaneously administered, self-injectable biologic treatment option approved for paediatric ulcerative colitis,” the researchers noted.

*ENVISION I: Efficacy and safety of adalimumab in pediatric subjects with moderate to severe ulcerative colitis

**high-dose induction adalimumab: 2.4 mg/kg (maximum of 160 mg) at weeks 0 and 1; standard-dose induction adalimumab: 2.4 mg/kg (maximum of 160 mg) at week 0 and matching placebo at week 1