P554 Incidence and impact of immunogenicity in a randomised, double-blind phase III study comparing a proposed infliximab biosimilar (PF-06438179/GP1111) with reference infliximab

Abstract

Background: Anti-drug antibodies (ADAs) have the potential to impact the pharmacokinetics (PK), efficacy and safety of biologic treatments, such as infliximab. With the recent availability of biosimilars, it is important to establish that immunogenicity and any associated impact is similar to that of the reference medicine. Methods: A multi-national, randomised, double-blind, parallelgroup study compared the efficacy, safety and immunogenicity of the proposed infliximab biosimilar, PF-06438179/GP1111, with the European reference infliximab (IFX-EU) in adult patients with moderate-to-severe active rheumatoid arthritis (RA) on a stable dose of methotrexate. Patients received 3 mg/kg IV dose of study treatment at Weeks 0, 2, 6 and then every 8 weeks, with a dose escalation to 5 mg/kg allowed from Week 14 for inadequate responders. The primary endpoint was a ≥20% improvement in American College of Rheumatology response (ACR20) at Week 14. Subgroup analyses by ADA status were conducted at Weeks 14 and 30. Serum PK samples were assayed using a validated ELISA. Blood samples were collected and assayed for ADA and neutralising antibodies (NAbs). Results: Six hundred and fifty patients were randomised (PF-06438179/GP1111, n = 324; IFX-EU, n = 326). ADAs were observed in 48.6% (n = 157) of patients with PF-06438179/GP111 and 51.2% (n = 167) with IFX-EU throughout 30 weeks, and NAbs were present in 79% (n = 124) and 85.6% (n = 143) of these patients, respectively. ACR20 response rates at Weeks 14 and 30 were similar between treatments regardless of ADA status. Serum concentrations of PF 06438179/GP1111 and IFX-EU were expectedly lower in patients with ADAs compared with those without. Importantly, serum concentrations were similar between treatment groups in ADA-positive patients. In each treatment group, n = 83 patients underwent dose escalation during the first 30 weeks of treatment and, in these patients, the ADA rates at Week 30 were similar (PF 06438179/GP1111, 45.8% vs. IFX-EU, 38.6%) and comparable to those patients not undergoing dose escalation (40.8% and 46.1%, respectively). Up to Week 30, infusion-related reactions (IRRs) occurred in 5.9% (n = 19 of 323) patients with PF 06438179/GP1111 and 6.4% (n = 21 of 326) with IFX-EU. In patients with ADAs, IRRs occurred in 7% (n = 11 of 157) with PF 06438179/GP1111 and 8.4% (n = 14 of 167) with IFX EU. Conclusions: Immunogenicity occurred at a similar frequency and had a similar impact on efficacy, PK and IRRs with PF 06438179/GP1111 compared with IFX EU in patients with moderate-to-severe active RA.