Characteristics of biological therapy in pediatric patients with Crohn’s disease

ABSTRACT

Introduction: At present, there is a significant amount of data related to biologics used in pediatric patients with Crohn’s disease. This review characterizes the different biological drugs administered in this population.

Areas covered: Biological therapy of CD, focusing on children, is summarized in this review. After mechanism of action and pharmacokinetics are described, mucosal healing on anti-TNF therapy, aspects of early therapy, long-term outcome and combination therapy are discussed. Moreover, loss of response and treatment optimization, as well as drug withdrawal are summarized. Subsequently, perianal disease and surgical aspects are discussed followed by safety issues. In addition, new drugs (vedolizumab, ustekinumab), cost-effectiveness and administration of biosimilars were also included.

Expert commentary: There are significant data to characterize biological drugs administered in pediatric patients with Crohn’s disease. However, head-to-head comparative studies using different biologics are missing.

KEYWORDS:

• Crohn’s disease
• pediatric
• biologics
• infliximab
• adalimumab
• vedolizumab
• ustekinumab
• biosimilars
• cost-benefit

Article highlights

• Childhood-onset CD has much worse phenotype and prognosis when compared to adult-onset with a shorter window of opportunity of medical treatment of inflammatory phenotype and increased need for surgical intervention due to penetrating or stricturing disease, therefore early aggressive treatment should be considered. Treat to target is one of the aims of the treatment using biological agents where mucosal healing with clinical remission (deep remission) can be achieved.

• For patients previously naïve to anti-TNF therapy, both IFX and ADA show comparable efficacy and adverse-events profile. There is no evidence that IFX is more effective than ADA in CD patients with fistula.

• Although anti-TNF antibodies are potent drugs up to 40% of patients are non-responders to induction and LOR in primary responders over time (from 6% to 46%) also leads to discontinuation of that particular drug. Combination therapy with an immunomodulator can decrease LOR and intensification of anti-TNF therapy with dose increase and/or interval shortening can help regaining response. Therapeutic drug monitoring with measurement of serum trough levels and antibodies is the key element of decision-making whether to optimize or stop therapy.

• There is insufficient evidence to define the risk/benefit ratio for mono- or combination therapy in all CD children, while it seems that combination therapy for the first 6 months may be associated with a lower rate of antibodies and LOR, this benefit should be weighed against the eventually increased lymphoma risk with thiopurines on an individual basis.

• Biosimilar (BS) (CT-P13) is a safe and efficacious alternative to the originator IFX for induction, and maintenance, of remission in children with IBD who are indicated for IFX treatment. To support a switch from the originator IFX to BS or starting BS as a first biological drug is supported by the economic benefit of BS, as it is suggested that price reduction could reach 60–70%.

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Declaration of interest

A Tarnok has received consultancy fees from AbbVie. G Veres has received consultancy fees from AbbVie and MSD. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.