A randomized controlled trial comparing PF-06438179/GP1111 (an infliximab biosimilar) and infliximab reference product for treatment of moderate to severe active ... View Full Text


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Article Info

DATE

2018-07-27

AUTHORS

Stanley B. Cohen, Rieke Alten, Hideto Kameda, Tomas Hala, Sebastiao C. Radominski, Muhammad I. Rehman, Ramesh Palaparthy, Karl Schumacher, Susanne Schmitt, Steven Y. Hua, Claudia Ianos, K. Lea Sewell

ABSTRACT

BACKGROUND: This double-blind, active-controlled, randomized, multinational study evaluated the efficacy, safety, pharmacokinetics (PK), and immunogenicity of PF-06438179/GP1111 (IxifiTM/Zessly®), an infliximab biosimilar, vs infliximab (Remicade®) reference product sourced from the European Union (infliximab-EU) in biologic-naïve patients with moderate to severe active rheumatoid arthritis (RA) despite methotrexate therapy. This paper reports results from the initial 30-week treatment period. METHODS: Patients (N = 650) were stratified by geographic region and randomized 1:1 to PF-06438179/GP1111 or infliximab-EU (3 mg/kg intravenous at weeks 0, 2, and 6, then every 8 weeks). Dose escalation to 5 mg/kg was allowed starting at week 14 for patients with inadequate RA response. The primary endpoint was American College of Rheumatology criteria for ≥ 20% clinical improvement (ACR20) response at week 14. Therapeutic equivalence was declared if the two-sided 95% CI for the treatment difference was within the symmetric equivalence margin of ± 13.5%. Statistical analysis was also performed with a two-sided 90% CI using an asymmetric equivalence margin (- 12.0%, 15.0%). RESULTS: Patients (80.3% female; 79.4% seropositive) had a mean RA duration of 6.9 years, and mean baseline Disease Activity Score in 28 joints, four components based on C-reactive protein was 6.0 in both arms. Week 14 ACR20 in the intention-to-treat population was 62.7% for PF-06438179/GP1111 and 64.1% for infliximab-EU. Week 14 ACR20 using nonresponder imputation was 61.1% for PF-06438179/GP1111 and 63.5% for infliximab-EU, and the 95% (- 9.92%, 5.11%) and 90% (- 8.75%, 4.02%) CIs for the treatment difference (- 2.39%) were entirely contained within the prespecified symmetric and asymmetric equivalence margins, respectively. No differences were observed between arms for secondary efficacy endpoints. Overall postdose antidrug antibody (ADA) rates through week 30 were 48.6% and 51.2% for PF-06438179/GP1111 and infliximab-EU, respectively. Efficacy and immunogenicity were similar between treatments for patients with dose escalation (at or after week 14), as well as between treatments for patients without dose escalation. Safety profiles of PF-06438179/GP1111 and infliximab-EU were similar, with no clinically meaningful differences observed between arms, including after ADA development. Serum drug concentrations were similar between arms at each time point during the initial 30-week treatment period. CONCLUSION: PF-06438179/GP1111 and infliximab-EU demonstrated similar efficacy, safety, immunogenicity, and PK with or without dose escalation in patients with moderate to severe active RA on background methotrexate. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02222493 . Registered on 21 August 2014. EudraCT, 2013-004148-49 . Registered on 14 July 2014. More... »

PAGES

155

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13075-018-1646-4

DOI

http://dx.doi.org/10.1186/s13075-018-1646-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1105875897

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30053896


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22 schema:description BACKGROUND: This double-blind, active-controlled, randomized, multinational study evaluated the efficacy, safety, pharmacokinetics (PK), and immunogenicity of PF-06438179/GP1111 (IxifiTM/Zessly®), an infliximab biosimilar, vs infliximab (Remicade®) reference product sourced from the European Union (infliximab-EU) in biologic-naïve patients with moderate to severe active rheumatoid arthritis (RA) despite methotrexate therapy. This paper reports results from the initial 30-week treatment period. METHODS: Patients (N = 650) were stratified by geographic region and randomized 1:1 to PF-06438179/GP1111 or infliximab-EU (3 mg/kg intravenous at weeks 0, 2, and 6, then every 8 weeks). Dose escalation to 5 mg/kg was allowed starting at week 14 for patients with inadequate RA response. The primary endpoint was American College of Rheumatology criteria for ≥ 20% clinical improvement (ACR20) response at week 14. Therapeutic equivalence was declared if the two-sided 95% CI for the treatment difference was within the symmetric equivalence margin of ± 13.5%. Statistical analysis was also performed with a two-sided 90% CI using an asymmetric equivalence margin (- 12.0%, 15.0%). RESULTS: Patients (80.3% female; 79.4% seropositive) had a mean RA duration of 6.9 years, and mean baseline Disease Activity Score in 28 joints, four components based on C-reactive protein was 6.0 in both arms. Week 14 ACR20 in the intention-to-treat population was 62.7% for PF-06438179/GP1111 and 64.1% for infliximab-EU. Week 14 ACR20 using nonresponder imputation was 61.1% for PF-06438179/GP1111 and 63.5% for infliximab-EU, and the 95% (- 9.92%, 5.11%) and 90% (- 8.75%, 4.02%) CIs for the treatment difference (- 2.39%) were entirely contained within the prespecified symmetric and asymmetric equivalence margins, respectively. No differences were observed between arms for secondary efficacy endpoints. Overall postdose antidrug antibody (ADA) rates through week 30 were 48.6% and 51.2% for PF-06438179/GP1111 and infliximab-EU, respectively. Efficacy and immunogenicity were similar between treatments for patients with dose escalation (at or after week 14), as well as between treatments for patients without dose escalation. Safety profiles of PF-06438179/GP1111 and infliximab-EU were similar, with no clinically meaningful differences observed between arms, including after ADA development. Serum drug concentrations were similar between arms at each time point during the initial 30-week treatment period. CONCLUSION: PF-06438179/GP1111 and infliximab-EU demonstrated similar efficacy, safety, immunogenicity, and PK with or without dose escalation in patients with moderate to severe active RA on background methotrexate. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02222493 . Registered on 21 August 2014. EudraCT, 2013-004148-49 . Registered on 14 July 2014.
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29 schema:keywords ACR20
30 ADA development
31 American College
32 College
33 Disease Activity Score
34 European Union
35 GP1111
36 NCT02222493
37 Overall postdose antidrug antibody (ADA) rates
38 PF-06438179/GP1111
39 RA duration
40 RA response
41 Rheumatology criteria
42 Union
43 Week 14 ACR20
44 active rheumatoid arthritis
45 activity score
46 analysis
47 antibody rates
48 antidrug antibody (ADA) rates
49 arm
50 arthritis
51 asymmetric equivalence margin
52 background
53 baseline Disease Activity Score
54 biologic-naïve patients
55 biosimilars
56 cis
57 clinical improvement (ACR20) response
58 components
59 concentration
60 criteria
61 development
62 differences
63 dose escalation
64 drug concentrations
65 duration
66 efficacy
67 efficacy endpoint
68 endpoint
69 equivalence
70 equivalence margin
71 escalation
72 geographic regions
73 immunogenicity
74 improvement response
75 imputation
76 inadequate RA response
77 infliximab biosimilar
78 infliximab reference product
79 infliximab-EU
80 intention
81 joints
82 margin
83 mean RA duration
84 meaningful differences
85 methotrexate therapy
86 multinational study
87 nonresponder imputation
88 paper
89 patients
90 period
91 pharmacokinetics
92 point
93 population
94 postdose antidrug antibody (ADA) rates
95 prespecified symmetric
96 primary endpoint
97 products
98 profile
99 protein
100 rate
101 reactive protein
102 reference product
103 region
104 response
105 results
106 rheumatoid arthritis
107 safety
108 safety profile
109 scores
110 secondary efficacy endpoints
111 serum drug concentrations
112 severe active rheumatoid arthritis
113 similar efficacy
114 statistical analysis
115 study
116 symmetric
117 symmetric equivalence margin
118 therapeutic equivalence
119 therapy
120 time points
121 treat population
122 treatment
123 treatment differences
124 treatment period
125 trials
126 vs infliximab (Remicade®) reference product
127 week 14
128 week 30
129 years
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