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Extrapolation of Adult Efficacy Data to Pediatric Systemic Lupus Erythematosus: Evaluating Similarities in Exposure-Response.

Publication ,  Journal Article
Balevic, SJ; Niu, J; Chen, J; Green, D; McMahon, A; Hornik, CP; Schanberg, LE; Glaser, R; Gonzalez, D; Burckart, GJ
Published in: J Clin Pharmacol
January 2023

To streamline drug development, the United States Food and Drug Administration (FDA) can consider the extrapolation of adult efficacy data to children when the disease and drug effects are sufficiently similar. This study explored whether the relationship between drug exposure and response for selected drugs in systemic lupus erythematosus (SLE) was sufficiently similar to support a consideration of the extrapolation of adult efficacy data to children of ≥5 years of age. An exposure-response analysis of drugs used to treat SLE was conducted using published exposure versus response and efficacy versus time data. Statistical analyses included noncompartmental analysis of a drug's area under the effect curve and direct Imax pharmacodynamic (PD) modeling. Six drugs were included: azathioprine, belimumab, cyclophosphamide, hydroxychloroquine, mycophenolate/mycophenolic acid, and rituximab. For belimumab, the net change in responders at week 52 (the primary end point) was nearly identical between 1 adult trial and the pediatric trial. For mycophenolate, PD modeling suggested no significant differences in exposure and SLE disease activity between adults and children. For azathioprine, cyclophosphamide, hydroxychloroquine, and rituximab the data were not sufficient to quantitatively characterize the exposure-response relationship, but the clinical or pharmacologic response between children and adults was similar overall. Adult SLE data should be leveraged to guide pediatric drug development programs and identify areas with residual uncertainty regarding the effectiveness or safety of a drug in children. The degree to which efficacy extrapolation can reduce clinical trial requirements in pediatric SLE should be individualized for each new drug product, depending in part on the mechanism of action of the drug and the similarity of disease manifestations in children and adults.

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Published In

J Clin Pharmacol

DOI

EISSN

1552-4604

Publication Date

January 2023

Volume

63

Issue

1

Start / End Page

105 / 118

Location

England

Related Subject Headings

  • Treatment Outcome
  • Rituximab
  • Pharmacology & Pharmacy
  • Lupus Erythematosus, Systemic
  • Immunosuppressive Agents
  • Hydroxychloroquine
  • Humans
  • Enzyme Inhibitors
  • Cyclophosphamide
  • Child
 

Citation

APA
Chicago
ICMJE
MLA
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Balevic, S. J., Niu, J., Chen, J., Green, D., McMahon, A., Hornik, C. P., … Burckart, G. J. (2023). Extrapolation of Adult Efficacy Data to Pediatric Systemic Lupus Erythematosus: Evaluating Similarities in Exposure-Response. J Clin Pharmacol, 63(1), 105–118. https://doi.org/10.1002/jcph.2139
Balevic, Stephen J., Jing Niu, Jianmeng Chen, Dionna Green, Ann McMahon, Christoph P. Hornik, Laura E. Schanberg, Rachel Glaser, Daniel Gonzalez, and Gilbert J. Burckart. “Extrapolation of Adult Efficacy Data to Pediatric Systemic Lupus Erythematosus: Evaluating Similarities in Exposure-Response.J Clin Pharmacol 63, no. 1 (January 2023): 105–18. https://doi.org/10.1002/jcph.2139.
Balevic SJ, Niu J, Chen J, Green D, McMahon A, Hornik CP, et al. Extrapolation of Adult Efficacy Data to Pediatric Systemic Lupus Erythematosus: Evaluating Similarities in Exposure-Response. J Clin Pharmacol. 2023 Jan;63(1):105–18.
Balevic, Stephen J., et al. “Extrapolation of Adult Efficacy Data to Pediatric Systemic Lupus Erythematosus: Evaluating Similarities in Exposure-Response.J Clin Pharmacol, vol. 63, no. 1, Jan. 2023, pp. 105–18. Pubmed, doi:10.1002/jcph.2139.
Balevic SJ, Niu J, Chen J, Green D, McMahon A, Hornik CP, Schanberg LE, Glaser R, Gonzalez D, Burckart GJ. Extrapolation of Adult Efficacy Data to Pediatric Systemic Lupus Erythematosus: Evaluating Similarities in Exposure-Response. J Clin Pharmacol. 2023 Jan;63(1):105–118.

Published In

J Clin Pharmacol

DOI

EISSN

1552-4604

Publication Date

January 2023

Volume

63

Issue

1

Start / End Page

105 / 118

Location

England

Related Subject Headings

  • Treatment Outcome
  • Rituximab
  • Pharmacology & Pharmacy
  • Lupus Erythematosus, Systemic
  • Immunosuppressive Agents
  • Hydroxychloroquine
  • Humans
  • Enzyme Inhibitors
  • Cyclophosphamide
  • Child