Pharmacokinetics, Pharmacodynamics, and Safety of Etrolizumab in Children With Moderately to Severely Active Ulcerative Colitis or Crohn's Disease: Results from a Phase 1 Randomized Trial.
Inflamm Bowel Dis
; 28(9): 1348-1356, 2022 09 01.
Article
en En
| MEDLINE
| ID: mdl-34849918
ABSTRACT
BACKGROUND:
Etrolizumab, a humanized anti-ß7 antibody, has not been studied in children. Here, we evaluate the pharmacokinetics, pharmacodynamics, and safety of etrolizumab in children with inflammatory bowel disease.METHODS:
Patients age 4 to 17 years with moderately to severely active ulcerative colitis or Crohn's disease were randomized 11 to receive 1.5mg/kg of etrolizumab subcutaneously every 4 weeks (q4w) or 3.0mg/kg every 8 weeks (q8w) for 16 weeks in this open-label phase 1 trial. Pharmacokinetics, pharmacodynamics, safety, and efficacy were assessed.RESULTS:
Of the 24 patients treated, 21 completed the study. In the groups of 1.5mg/kg q4w and 3.0mg/kg q8w, respectively, mean (SD) maximum concentration (Cmax) was 9.8 (4.86) µg/mL and 18.1 (6.25) µg/mL; and mean (SD) area under the curve within a dosing interval (AUCtau) was 167 (86.9) and 521 (306) µg·day/mL after the last dose. The Cmax increased dose proportionally. The AUC over an 8-week period was slightly higher in the 3.0mg/kg q8w dose group. Median half-life was similar for both dosing regimens. Median numbers of free ß7high gut-homing T and B cell subsets declined below 10% of baseline, confirming ß7 target engagement and complete/near-complete receptor occupancy. Adverse events were consistent with the safety profile in adults. Approximately 60% of patients achieved a clinical response.CONCLUSIONS:
Etrolizumab showed a dose-proportional increase in Cmax and a slightly greater than dose-proportional increase in AUCtau. Both regimens achieved complete/near-complete ß7 receptor occupancy, with a similar relationship to concentration as adults. Etrolizumab was well tolerated and demonstrated clinical activity in children.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades Inflamatorias del Intestino
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Colitis Ulcerosa
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Enfermedad de Crohn
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Adolescent
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Adult
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Child
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Child, preschool
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Humans
Idioma:
En
Revista:
Inflamm Bowel Dis
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos