Intest Res.  2021 Apr;19(2):217-224. 10.5217/ir.2019.09164.

Ustekinumab for the treatment of refractory pediatric Crohn’s disease: a single-center experience

• Cohen A
• Ahmed N
• Sant’Anna A

• KMID: 2515480
• DOI: http://doi.org/10.5217/ir.2019.09164

Abstract

Background/Aims
Despite the well-established efficacy of tumor necrosis factor (TNF) antagonists as treatment options for Crohn’s disease, many pediatric patients need a change in therapy due to adverse events and loss of response, highlighting the necessity for medications with a different mechanism of action. Ustekinumab has been shown to be effective in inducing clinical remission in some adults with disease refractory to anti-TNF agents, however, minimal data exists in the pediatric population.
Methods
We conducted a retrospective chart review of 11 pediatric patients receiving ustekinumab, specifically extracting baseline data, information on prior treatment and response, indications for starting ustekinumab, clinical information, and laboratory parameters pre- and post-therapy. Clinical response was defined as a decrease in abbreviated Pediatric Crohn’s Disease Activity Index score.
Results
Patients ranged from 12 to 17 years of age upon initiation of treatment with ustekinumab. Five of 11 patients demonstrated a clinical response. Among these patients, 2 remained in clinical remission, while the remaining 3 experienced a secondary loss of response. The other 6 patients were primary nonresponders who either remained unwell or demonstrated slight clinical worsening. All patients who clinically responded to ustekinumab and had an initially elevated CRP experienced complete normalization of their values. Mucosal healing was seen on endoscopy in 1 responder, with 2 other patients showing endoscopic improvement.
Conclusions
These results demonstrate for the first time that ustekinumab has the potential to induce not only clinical and biochemical remission, but also endoscopic improvement, in the pediatric population. Future research is needed to determine factors that influence response to therapy.

Keyword

Inflammatory bowel disease; Mucosal healing; Remission; Clinical improvement; Inflammatory markers

Figure

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  Fig. 1. Abbreviated Pediatric Crohn’s Disease Activity Index (abbrPCDAI) scores over time. (A) Ustekinumab responders and (B) ustekinumab nonresponders. When more than one abbrPCDAI score was recorded in a given timeframe, all calculated scores were averaged together. Patients 7 and 10 were categorized as nonresponders despite low abbrPCDAI scores due to significant inflammation seen on imaging or endoscopy both before initiation of therapy and upon termination.

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  Fig. 2. Change in weight over the course of ustekinumab therapy. (A) Ustekinumab responders and (B) ustekinumab nonresponders. When more than one weight was recorded in a given timeframe, all calculated scores were averaged together. Patient 2 was excluded due to intentional weight loss over the course of ustekinumab therapy. Patients 4, 5, 9, and 11 were taking concomitant corticosteroids.

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  Fig. 3. Change in C-reactive protein (CRP) over the course of ustekinumab therapy. All patients with normal CRP values at baseline pre-ustekinumab despite elevated abbreviated Pediatric Crohn’s Disease Activity Index scores were excluded from this graph.

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