The Efficacy and Evidence-Based Use of Biologics in Children and Adolescents: Using Monoclonal Antibodies and Fusion Proteins as Treatments

Dtsch Arztebl Int. 2019 Oct 18;116(42):703-710. doi: 10.3238/arztebl.2019.0703.

Abstract

Background: Monoclonal antibodies (mAb) and fusion proteins (FP) are increasingly being used in children and adolescents. In this review, we analyze the evidence for their safety and efficacy in the treatment of the most common chronic inflammatory diseases.

Methods: We systematically searched PubMed, AWMF.org, and other databases for high-quality trials (i.e., randomized controlled trials with clinical primary endpoints) and guidelines published at any time up to 10 December 2018 that dealt with mAb and FP that are approved for pediatric use. The search term was "monoclonal anti- body/fusion protein [e. g. adalimumab] AND children."

Results: The 620 hits included 25 high-quality trials (20 of them manufacturer- sponsored) on 9 mAb/FP (omalizumab, adalimumab, etanercept, ustekinumab, infliximab, golimumab, anakinra, canakinumab, tocilizumab, and abatacept), as well as 6 guidelines (3 each of levels S3 and S2k) on the treatment of bronchial asthma, psoriasis, juvenile idopathic arthritis, and chronic inflammatory bowel diseases. For none of these conditions are mAb and FP the drugs of first choice. Adverse drug effects are rare but sometimes severe (infection, immune dysregulation, tumors).

Conclusion: The retrieved trials have deficiencies that make it difficult to reliably evaluate the efficacy, safety, and utility of mAb/FP for children and adolescents with chronic inflammatory diseases. mAb/FP nonetheless represent a treatment option to be considered in case conventional immune-modulating drugs are ineffective. Researcher-initiated, high-quality trials and manufacturer-independent, systematic long-term evaluations of adverse effects (e.g., tumors) are sorely needed.

Publication types

  • Systematic Review

MeSH terms

  • Adolescent
  • Antibodies, Monoclonal / therapeutic use*
  • Biological Products / therapeutic use*
  • Child
  • Humans
  • Proteins / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Biological Products
  • Proteins