Session Information
Date: Tuesday, October 23, 2018
Title: Rheumatoid Arthritis – Treatments Poster III: Biosimilars and New Compounds
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: PF-06438179/GP1111 (IFX-PF) is an infliximab (IFX) biosimilar for the treatment of immune-mediated inflammatory diseases, including RA. This randomized, double-blind, comparative clinical study evaluated the efficacy, safety and immunogenicity of IFX-PF and IFX reference product sourced from the European Union (IFX-EU) in patients (pts) with moderate to severe active RA with inadequate response to MTX and ≤2 doses of 1 non-depleting, non-IFX biologic (NCT02222493). We report results from Week (Wk) 54 to Wk 78.
Methods: Pts (N=650), stratified by geographic region, were initially randomized (1:1) in treatment period 1 (TP1) to IFX-PF or IFX-EU (3 mg/kg IV at Wks 0, 2, 6, and then every 8 wks), both given with MTX (10–25 mg/wk). The primary endpoint was ACR20 at Wk 14. Secondary efficacy endpoints included ACR20 (other than at Wk 14), DAS28-CRP and other measures of clinical response or remission. At Wk 30 (beginning of TP2), patients receiving IFX-EU were blindly re-randomized (1:1) to remain on IFX-EU or transition to IFX-PF for 24 wks. During TP3 (beginning at Wk 54), all pts received open-label treatment with IFX-PF; 3 groups were evaluated in TP3 corresponding to the treatment sequence (TP1/TP2/TP3) during the study: IFX-PF/IFX-PF/IFX-PF; IFX-EU/IFX-EU/IFX-PF; IFX-EU/IFX-PF/IFX-PF.
Results: Of the pts initially randomized (TP1) (IFX-PF, n=324; IFX-EU, n=326), 566 pts entered TP2 at Wk 30. At Wk 54, all pts remaining on IFX-EU were switched to IFX-PF; 505 pts continued to participate in TP3. The majority of TP3 pts were female (79.2%) and White (78.6%). ACR20 response rates and DAS28-CRP scores were sustained and comparable across the 3 groups during TP3 (Table). IFX-PF was well tolerated during TP3; the safety profile was comparable across all 3 groups. Incidence of treatment-emergent adverse events during TP3 was 29.3% overall and 28.9% (IFX-PF/IFX-PF/IFX-PF), 30.2% (IFX-EU/IFX-EU/IFX-PF), and 29.4% (IFX-EU/IFX-PF/IFX-PF); the incidence of infusion-related reactions was 2.0% overall and 1.2%, 3.2% and 2.4% in the 3 groups, respectively. Pre-dose (TP3) anti-drug antibody (ADA) rates at Wk 54 were 44.3%, 47.6% and 53.2% for the IFX-PF/IFX-PF/IFX-PF, IFX-EU/IFX-EU/IFX-PF and IFX-EU/IFX-PF/IFX-PF groups, respectively. The incidences of pts with a first positive ADA result occurring during TP3 (6.0%, 8.0% and 6.4% for the IFX-PF/ IFX-PF/IFX-PF, IFX-EU/IFX-EU/IFX-PF and IFX-EU/IFX-PF/IFX-PF groups, respectively) and overall, post-dose ADA rates in TP3 (56.9%, 63.5%, and 65.1%, respectively) were comparable among groups.
Conclusion: In line with earlier findings from this study, results from TP3 (Wks 54–78) show the absence of clinically meaningful differences in efficacy, safety and immunogenicity between treatment groups, independent of a single treatment transition from IFX-EU to IFX-PF at Wk 30 or Wk 54.
Table
|
ACR20 Response by Visit (TP3 ITT Population), n (%) |
||||
|
Week |
IFX-PF/IFX-PF/IFX-PF |
IFX-EU/IFX-EU/IFX-PF |
IFX-EU/IFX-PF/IFX-PF |
Total (N = 505) |
|
54 |
197 (77.9) |
90 (71.4) |
99 (78.6) |
386 (76.4) |
|
78 |
192 (75.9) |
86 (68.3) |
98 (77.8) |
376 (74.5) |
|
DAS28-CRP Score by Visit (TP3 ITT Population), mean (SD) |
||||
|
Week |
IFX-PF/IFX-PF/IFX-PF |
IFX-EU/IFX-EU/IFX-PF |
IFX-EU/IFX-PF/IFX-PF |
Total (N = 501) |
|
54 |
3.4 (1.32) |
3.6 (1.35) |
3.6 (1.26) |
3.5 (1.32) |
|
78 |
3.1 (1.28) |
3.3 (1.30) |
3.3 (1.23) |
3.2 (1.27) |
|
Abbreviations: DAS28-CRP, Disease Activity Score-28; 4 components based on high-sensitivity C-reactive protein; IFX-EU, infliximab reference product sourced from the European Union; ITT, intent to treat; N, number of subjects in the TP3 ITT population; n, number of subjects; IFX-PF, PF-06438179/GP1111; SD, standard deviation; TP3, treatment period 3. |
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To cite this abstract in AMA style:
Cohen S, Kivitz AJ, Tee M, Cronenberger C, Zhang M, Hackley S, Schumacher K, Rehman MI. A Randomized, Double-Blind Phase III Study Comparing the Efficacy, Safety and Immunogenicity of PF-06438179/GP1111 (Ixifi™), an Infliximab Biosimilar, and Infliximab Reference Product (Remicade®) in Patients with Moderate to Severe Active RA: Results from Week 54 to Week 78 [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/a-randomized-double-blind-phase-iii-study-comparing-the-efficacy-safety-and-immunogenicity-of-pf-06438179-gp1111-ixifi-an-infliximab-biosimilar-and-infliximab-reference-product-remicad/. Accessed .« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-randomized-double-blind-phase-iii-study-comparing-the-efficacy-safety-and-immunogenicity-of-pf-06438179-gp1111-ixifi-an-infliximab-biosimilar-and-infliximab-reference-product-remicad/