Introduction: Dose escalation (DE) of subcutaneous (SC) infliximab from 120 mg to 240 mg every 2 weeks (Q2W) showed restoring efficacy in the 54-week LIBERTY-CD and LIBERTY-UC studies, and safety profiles were generally comparable between patients with or without DE. Both two studies included an extension phase through Week (W) 102, and we present post-hoc long-term efficacy and safety results of DE in patients who treated in extension phase in two studies. Aims & Methods: Patients with moderately to severely active CD and UC were treated with 3 doses of infliximab IV 5 mg/kg as induction therapy (Weeks 0, 2 and 6). Clinical responders at W10 were randomized (2:1) to receive either CT-P13 SC 120 mg or placebo Q2W as maintenance therapy up to W54. Patients who would benefit from continued treatment entered open-label extension study from W56 to W102 by the opinion of the investigator received CT-P13 SC 120 mg regardless of previously assigned arm. From W22, the patients who met loss of response criteria were permitted to escalate the dose to CT-P13 SC 240 mg Q2W through W102 for both arms. The results from CT-P13 SC arm treated in extension phase are analyzed.
Results: A total of 192 and 237 patients were analyzed in CD and UC study, each. Among them, DE from CT-P13 SC 120 mg to CT-P13 SC 240 mg prior to W102 was more common in UC than CD (30.0% [71/237] vs 21.9% [42/192]). Patients showed improvement in clinical remission at W102 (both CD and UC) or endoscopic response at W102 (CD) after DE. Also, patients showed improvement in other efficacy endpoints after DE (Table 1). Most patients with DE regained clinical remission and clinical response within 8 weeks after DE (Table 2). For UC, endpoints were defined by modified Mayo score in Table 1, partial Mayo score in Table 2, respectively. The incidence rate of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) in the pooled safety data (CD+UC) across maintenance and extension phase were comparable between patients with and without DE (85.2% [98/115] vs 78.8% [256/325] for TEAEs, 13.0% [15/115] vs 10.5% [34/325] for TESAEs). The incidence rate of TEAEs of infection for patients with and without DE was 45.2% [52/115] vs 43.4% [141/325]. The incidence rate of TEAEs of systemic injection reaction for patients with and without DE was 4.3% [5/115] vs 2.8% [9/325]. Conclusion: DE of CT-P13 SC from 120 mg to 240 mg Q2W in patients who initially respond but subsequently lose response, shows improving clinical efficacy over an extended observation period of 102 weeks. Most patients with DE regained response promptly within 8 weeks after DE. Safety profiles were generally comparable between patients with or without DE, and no new safety concerns were found after DE as well in long term treatment.
