P396 Pharmacokinetics, immunogenicity and clinical outcomes of golimumab from the PURSUIT PEDS ulcerative colitis study long-term (through week 126) extension

Abstract Background To evaluate the pharmacokinetics (PK) and immunogenicity of the anti-TNF golimumab (GLM) in children with ulcerative colitis (UC) from the PURSUIT PEDS PK study long-term extension (LTE). Methods A multicentre open-label study was performed to assess the PK, immunogenicity, efficacy, and safety of GLM in children 2–17 years with moderate-to-severe UC (Mayo score 6–12, endoscopy subscore ≥2), unresponsive to prior treatments and naïve to anti-TNF. At week 14 (LTE week 0), 20 week 6 Mayo responders continued GLM maintenance every 4 weeks. Patients ≥45 kg were eligible for at-home administration starting Week 18. PK, the presence of anti-nuclear antibodies (ANA) and anti-GLM antibodies, and clinical outcomes, were determined through Week 126. Patients who, while in the LTE, received GLM and had 1 or more suitable samples were included in the PK and immunogenicity analyses. Results Of the 35 children enrolled at week 0, 21 (60%) achieved Mayo response at week 6, and 20 entered the LTE at week 14. Of these, 9 (45%), 11 (55%), and 10 (50%) were in PUCAI remission at weeks 30, 54, and 126, respectively. Of the 375 total injections during the LTE, 162 (43.2%) were given at home, the majority of those being self-administered. No anaphylactic or serum sickness-like reactions, opportunistic infections, malignancies or deaths were reported. Of the 20 patients included in the PK and immunogenicity analyses, all had detectable drug levels at least once from week 14 through week 126. Observed trough values were consistent over time through week 126, except for week 110, which had a higher median concentration, potentially due to the small sample size at this visit. The incidence of anti-GLM antibodies increased from 10% (2/20) at week 30 to 25.0% (5/20) at week 126; only one subject was positive for neutralising antibodies. Maximum titers from week 30 of 1:24 and 1:96 did not change through week 126. The remaining three patient’s titers were 1:6. Two of 18 (11.1%) patients tested positive for ANA at week 0 and remained positive through week 126 (titer ≥1:160). No other subjects developed ANA antibodies during the LTE. No patient was positive for anti-dsDNA antibodies at any time. Conclusions Children with UC who received GLM q4w maintenance showed continued clinical benefit through week 126 in this open-label study. Trough values with maintenance SC GLM treatment q4w through week 126 were consistent over the extended treatment time. Antibodies to GLM