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.

Conflict of interest statement

SBC has received research grants and consulting fees or honorarium from AbbVie, Amgen, Pfizer, and Sandoz. RA has no conflicts of interest that are directly relevant to the content of this article. HK has received consulting fees, speaking fees, and/or honoraria from AbbVie GK, Asahi Kasei Pharma, Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly Japan KK, Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma, Novartis, and Pfizer Japan and has received research grants from AbbVie GK, Asahi Kasei Pharma, Astellas Pharma, Chugai Pharmaceutical, Eisai, Mitsubishi Tanabe Pharma, and Novartis. AJK has received consulting fees and/or speaking fees and/or fees for participation on advisory committees or review panels from Sanofi, Regeneron, SUN Pharma Advanced Research, AbbVie, Janssen, Pfizer, UCB, Genzyme, Boehringer-Ingelheim, Celgene, Horizon, Merck, Novartis, and Flexion and has stock holdings for Pfizer, Sanofi, Amgen, and Gilead. MT has received research grants, speaking fees, and honoraria from Pfizer Philippines. SCR has received research grants from Pfizer. OvR is an employee of Hexal AG (a Sandoz company). CC, SH, MIR, and MZ are employees of, and hold stock or stock options from, Pfizer.

Figures

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