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A randomized controlled trial comparing PF-06438179/GP1111 (an infliximab biosimilar) and infliximab reference product for treatment of moderate to severe active rheumatoid arthritis despite methotrexate therapy

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Cohen SB1, Alten R2, Kameda H3, Hala T4, Radominski SC5, Rehman MI6, Palaparthy R7, Schumacher K8, Schmitt S8, Hua SY7, Ianos C9, Sewell KL10. Arthritis Res Ther. 2018 Jul 27;20(1):155. doi: 10.1186/s13075-018-1646-4.


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1 Metroplex Clinical Research Center, 8144 Walnut Hill Lane, Suite 810, Dallas, TX, 75231, USA. arthdoc@aol.com.

2 Schlosspark-Klinik University Medicine, Heubnerweg 2, 14059, Berlin, Germany.

3 Toho University Ohashi Medical Center, 2-17-6, Ohashi Muguro-ku, Tokyo, 153-8515, Japan.

4 Center for Clinical and Basic Research, Trida Miru 2800, 530 02, Pardubice, Czech Republic.

5 Universidade Federal do Paraná, Rua General Carneiro, 181 - Alto da Glória, Curitiba, PR, 80.060-900, Brazil.

6 Pfizer Inc., 1 Burtt Road, Andover, MA, 01810, USA.

7 Pfizer Inc., 10777 Science Center Drive, CB1/2103, San Diego, CA, 92121, USA.

8 Hexal AG, Industriestraße 25, D-83607, Holzkirchen, Germany.

9 Pfizer UK, Discovery Park, Ramsgate Road, Sandwich, CT13 9ND, UK.

10 Pfizer Inc., 300 Technology Square, Cambridge, MA, 02139, USA.


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.