Poster #072: Population Pharmacokinetics and Exposure-Response Modeling Analyses of Golimumab in Pediatric Patients With Moderate-to-Severe Ulcerative Colitis

摘要

Statement of Purpose, Innovation or Hypothesis: Golimumab, a fully-human anti-TNFa monoclonal antibody, is approved for the treatment of adults with moderate-to-severe ulcerative colitis (UC) and is currently being investigated in pediatric patients with UC. Population pharmacokinetics (PK) and exposure-response (E-R) modeling analyses were conducted to assess the similarities of PK and E-R relationship of golimumab between pediatric and adult patients with UC and to subsequently support dosing recommendations for the pediatric UC population. Description of Methods and Materials: Golimumab PK data through Week 14 of subcutaneous golimumab administration from the PURSUIT PEDS PK Study, along with existing golimumab PK data from the adult UC and pediatric polyarticular juvenile idiopathic arthritis (pJIA) studies, were utilized for the population PK analysis using NONMEM. Existing golimumab PK data from other relevant populations was used to supplement and enhance the small data set from the pediatric UC study in the development of the PK model. Logistic regression of the E-R data from the pediatric and adult UC studies was conducted to explore the relationship between systemic golimumab exposure at Week 6 and induction efficacy outcomes (including clinical response, clinical remission and mucosal healing as measured by Mayo score) at Week 6. Data and Results: Golimumab PK was adequately described by a one-compartment linear model. Body weight, albumin, concurrent methotrexate use and antibody to golimumab status were statistically-significant covariates of golimumab PK. The PK characteristics of golimumab in pediatric UC patients were comparable to those in adults and were not influenced by age after adjusting for body weight. E-R modeling results suggest that E-R relationships between golimumab serum concentration and induction efficacy outcomes at Week 6 were generally comparable between pediatric and adult patients with UC, although pediatric patients appeared to be more responsive to golimumab treatment. Interpretation, Conclusion or Significance: Golimumab PK and E-R were generally comparable between pediatric and adult UC patients, supporting the extrapolation of efficacy of golimumab from adults to pediatric patients with UC.