Controlled Clinical Trials in Humans
Aram Kang, PharmD (she/her/hers)
Medical Communications Specialist
Celltrion
Incheon, Republic of Korea
Background
The Phase 3 LIBERTY-UC study (NCT04205643) demonstrated that subcutaneous (SC) CT-P13 had superior efficacy to placebo as maintenance therapy and was well tolerated in patients with moderately-to-severely active ulcerative colitis (UC) who responded to intravenous CT‑P13 induction. This post hoc analysis investigated whether the presence of anti-drug antibodies (ADAs) impacted efficacy and/or drug levels in patients treated with CT-P13 SC during LIBERTY-UC.
Methods
This post hoc analysis evaluated the impact of ADAs on clinical outcomes in patients with UC who received CT-P13 SC maintenance treatment. Presence and titer of ADA were measured using a new generation, highly sensitive, drug-tolerant assay. The following clinical outcomes were evaluated at Week (W) 54 according to ADA occurrence: clinical remission, clinical response, endoscopic-histologic mucosal improvement, and corticosteroid-free remission. Persistence up to W54, as well as safety and serum infliximab concentrations were assessed according to ADA occurrence. The ADA-positive population was further divided according to relative titers of ADA at W54 and analyzed for the clinical outcomes.
Results
The analysis included 294 patients with UC (ADA-positive, n=187; ADA-negative, n=107) who were randomized to CT-P13 SC maintenance at W10. Baseline characteristics were comparable between ADA-positive and ADA-negative groups (Table). There were no statistically significant differences in efficacy outcomes at W54 between the ADA-positive and ADA-negative patients across imputation methods. Based on observed data at W54 in the ADA-negative vs. ADA‑positive groups, 45.8% vs 41.7% achieved clinical remission (p=0.5413); 50.5% vs. 55.6% achieved clinical response (p=0.3982); 37.4% vs. 34.8% achieved endoscopic-histologic mucosal improvement (p=0.7047); and 40.7% vs 33.3% achieved corticosteroid-free remission (p=0.4493). In a survival analysis, 1-year persistence was comparable between the ADA-positive and ADA-negative groups (log-rank p= 0.12; Figure). Safety data were also generally comparable between the two groups. From W6 to W54, mean serum infliximab concentrations ranged from 11.8 to 13.9 µg/mL in ADA-positive patients, and from 15.2 to 21.3 µg/mL in ADA-negative patients, respectively. In the subgroup analysis by ADA titer at W54, patients with ADA titers ≥ 1,000 achieved efficacy outcomes at lower rates compared to those with lower ADA titers.
Conclusions
While results by ADA occurrence did not indicate significant difference in efficacy and persistence, the subgroup analysis by titer revealed that patients with higher ADA titers showed a diminished clinical response. Further studies are warranted focusing on longer-term effects of immunogenicity using data from the extension study of LIBERTY-UC and titer thresholds that can affect clinical outcomes and drug pharmacokinetics.