Long-term Efficacy, Safety, and Immunogenicity of the Infliximab (IFX) Biosimilar, PF-06438179/GP1111, in Patients with Rheumatoid Arthritis After Switching from Reference IFX or Continuing Biosimilar Therapy: Week 54-78 Data From a Randomized, Double-Blind, Phase III Trial

Abstract

Objective: Our objective was to evaluate the long-term efficacy, safety, and immunogenicity of the infliximab biosimilar, PF-06438179/GP1111 (PF-SZ-IFX), in patients with rheumatoid arthritis (RA) who continued biosimilar treatment throughout 78 weeks or who switched from reference infliximab (Remicade^®) sourced from the EU (IFX-EU) at week 30 or week 54 in the REFLECTIONS B537-02 study.

Methods: In this phase III, double-blind, active-controlled study, patients with moderate-to-severe active RA were initially randomized to PF-SZ-IFX or IFX-EU, each with methotrexate (treatment period [TP] 1; N = 650). At week 30, patients receiving PF-SZ-IFX continued PF-SZ-IFX; patients receiving IFX-EU were re-randomized to continue IFX-EU or switch to PF-SZ-IFX (TP2; n = 566). From weeks 54 to 78, all patients received open-label treatment with PF-SZ-IFX (TP3; n = 505). Efficacy, safety, and immunogenicity data were analyzed during TP3.

Results: Efficacy was sustained and comparable across groups at week 78, with American College of Rheumatology criteria for ≥ 20% clinical improvement response rates of 75.9% (biosimilar group), 77.8% (week 30 switch group), and 68.3% (week 54 switch group). The incidence of treatment-emergent adverse events was 28.9%, 29.4%, and 30.2%, respectively. The proportion of patients who were antidrug antibody (ADA) positive and neutralizing antibody positive (as a percentage of ADA-positive patients) was stable and comparable between groups.

Conclusions: Results to week 78 continue to support the efficacy, safety, and immunogenicity of PF-SZ-IFX in patients with moderate-to-severe active RA. There were no clinically meaningful differences between groups, independent of a single treatment transition from IFX-EU to PF-SZ-IFX at week 30 or week 54.

Trial registration number: NCT02222493.

Fig. 1

Study design. ^aStratified according to geographic region (North America and Western Europe, Japan, Republic of Korea, Latin America, and the rest of the world). ^b3 mg/kg intravenously. The treatment dose could be increased to 5 mg/kg and the escalated dose maintained in patients with an inadequate response at or after week 14. ^cIn a blinded manner, without stratification. EOT end of treatment, IFX-EU reference infliximab sourced from the EU, PF-SZ-IFX PF-06438179/GP1111, RA rheumatoid arthritis

Fig. 2

Proportions of patients achieving a ACR20/50/70 responses, b good EULAR response, c DAS28-CRP remission, and d ACR/EULAR remission during TP3. ITT population in TP3. ACR20/50/70 20%/50%/70% improvement in American College of Rheumatology response from study baseline (week 0), DAS28-CRP Disease Activity Score in 28 joints based on high-sensitivity C-reactive protein, EULAR European League Against Rheumatism, ITT intent-to-treat, TP3 treatment period 3

Fig. 3

Mean changes from study baseline (week 0) in a DAS28-CRP and b HAQ-DI during TP3. ITT population in TP3. DAS28-CRP Disease Activity Score in 28 joints based on high-sensitivity C-reactive protein, HAQ-DI Health Assessment Questionnaire—Disability Index, ITT intent-to-treat, SE standard error

Fig. 4

The proportions of patients who tested positive for ADAs and, of those, the proportions who tested positive for NAbs, by study visit in TP3. ^aNAb-positive incidences are expressed as percent of ADA-positive patients. ADA antidrug antibody, NAb neutralizing antidrug antibody, TP3 treatment period 3