ABSTRACT Background and Aims LIBERTY‐CD and LIBERTY‐UC demonstrated superior efficacy of subcutaneous infliximab (IFX SC) to placebo in patients with Crohn's disease (CD) or ulcerative colitis (UC). Here, we investigated the impact of anti‐drug antibodies (ADAs) on clinical outcomes. Methods Patients randomized to IFX SC maintenance treatment in the LIBERTY trials were included (CD, n = 231; UC, n = 294). ADAs were tested using a highly sensitive, drug‐tolerant assay. Patients were grouped by ADA occurrence and titer and evaluated for outcomes up to Week (W) 54. Results Among patients with CD and UC, 150 (64.9%) and 187 (63.6%) were ADA‐positive, respectively. No statistically significant differences were observed between the ADA‐positive and ADA‐negative groups in W54 efficacy (CD: clinical remission, 69.5% 95% confidence interval: 61.6–77.5 vs. 79.7% 70.2–89.2, p = 0.134; endoscopic response, 57.5% 48.9–66.1 vs. 65.2% 54.0–76.5, p = 0.359; UC: clinical remission, 49.1% 41.3–56.8 vs. 57.0% 46.5–67.4, p = 0.284), drug persistence (CD: 84.7% 79.1–90.6 vs. 85.2% 77.8–93.3; UC: 84.5% 79.5–89.8 vs. 77.6% 70.1–85.9), and safety (patients with ≥ 1 treatment‐emergent adverse event; CD: 71.2% 64.0–78.3 vs. 74.4% 64.9–83.8; UC: 69.5% 62.9–76.0 vs. 64.2% 55.0–73.3), despite lower drug concentrations in ADA‐positive patients at W54 (CD: 10.6 μg/mL 9.1–12.2 vs. 17.9 μg/mL 15.8–20.1; UC: 12.2 μg/mL 10.8–13.5 vs. 21.0 μg/mL 18.4–23.6). No significant relationship between ADA titer and efficacy or persistence was noted. Conclusions Although ADAs affected drug levels, no significant differences by ADA occurrence were observed in W54 efficacy or safety among patients receiving IFX SC maintenance treatment. While high ADA titers were associated with lower drug levels, effectiveness was not diminished within 1 year. Trial Registration ClinicalTrials.gov identifiers NCT03945019 (LIBERTY‐CD) and NCT04205643 (LIBERTY‐UC)
Colombel et al. (Wed,) studied this question.