Article

A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study

Division of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
Annals of the rheumatic diseases (Impact Factor: 9.27). 05/2013; 72(10). DOI: 10.1136/annrheumdis-2012-203090
Source: PubMed

ABSTRACT OBJECTIVES: To compare the efficacy and safety of innovator infliximab (INX) and CT-P13, an INX biosimilar, in active rheumatoid arthritis patients with inadequate response to methotrexate (MTX) treatment. METHODS: Phase III randomised, double-blind, multicentre, multinational, parallel-group study. Patients with active disease despite MTX (12.5-25 mg/week) were randomised to receive 3 mg/kg of CT-P13 (n=302) or INX (n=304) with MTX and folic acid. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 30. Therapeutic equivalence of clinical response according to ACR20 criteria was concluded if the 95% CI for the treatment difference was within ±15%. Secondary endpoints included ACR response criteria, European League Against Rheumatism (EULAR) response criteria, change in Disease Activity Score 28 (DAS28), Medical Outcomes Study Short-Form Health Survey (SF-36), Simplified Disease Activity Index, Clinical Disease Activity Index, as well as pharmacokinetic (PK) and pharmacodynamic (PD) parameters, safety and immunogenicity. RESULTS: At week 30, ACR20 responses were 60.9% for CT-P13 and 58.6% for INX (95% CI -6% to 10%) in the intention-to-treat population. The proportions in CT-P13 and INX groups achieving good or moderate EULAR responses (C reactive protein (CRP)) at week 30 were 85.8% and 87.1%, respectively. Low disease activity or remission according to DAS28-CRP, ACR-EULAR remission rates, ACR50/ACR70 responses and all other PK and PD endpoints were highly similar at week 30. Incidence of drug-related adverse events (35.2% vs 35.9%) and detection of antidrug antibodies (48.4% vs 48.2%) were highly similar for CT-P13 and INX, respectively. CONCLUSIONS: CT-P13 demonstrated equivalent efficacy to INX at week 30, with a comparable PK profile and immunogenicity. CT-P13 was well tolerated, with a safety profile comparable with that of INX. CLINICALTRIALS.GOV IDENTIFIER: NCT01217086.

1 Follower
 · 
190 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Biological agents for inflammatory bowel diseases (IBD) targeting tumor necrosis factor (TNF) have changed the way to treat IBD refractory to standard medications and allowed us to reach new therapeutic goals such as mucosal healing and deep remission. A better understanding of the components of the pathological processes that are a hallmark of IBD has led to the development of a new family of biological agents in Crohn's disease and ulcerative colitis. Biosimilars, which are copy versions of currently licensed biological agents, will be soon available. The biosimilar of infliximab is as effective and as safe as its originator in rheumatologic conditions, while a new anti-TNF agent, namely golimumab, has been recently approved for refractory ulcerative colitis. Beyond TNF blockers, anti-adhesion molecules appear to be a potent drug class for IBD. Vedolizumab was recently approved for both Crohn's disease and ulcerative colitis. Numerous other compounds are in the pipeline. Ustekinumab looks very promising for Crohn's disease. Smad7 antisense oligonucleotide might enrich our armamentarium if preliminary data are confirmed in upcoming clinical trials. Herein, we review the efficacy and safety of new and emerging biological agents that are currently investigated in IBD clinical trials.
    Therapeutic Advances in Gastroenterology 03/2015; 8(2):66-82. DOI:10.1177/1756283X14558193
  • [Show abstract] [Hide abstract]
    ABSTRACT: Biosimilars are biologic medical products whose active drug substance is made by a living organism or derived from it. The term is used to describe a subsequent version of an innovator biopharmaceutical product aiming at approval following patent expiry on the reference product. Biosimilars of monoclonal need to demonstrate similar but not identical quality of nonclinical and clinical attributes. Not all data of the originator product need to be recapitulated, as large numbers of patient-years of exposure data are already available. Thus, biosimilar development is largely based on the safety profiles of the originator product. The evaluation of biosimilarity includes immunogenicity attributed risks. CT-P13 (Remsima™/Inflectra™, Celltrion/Hospira), a biosimilar of the innovator drug infliximab (INF), was the first approved complex biosimilar monoclonal antibody in the EU, within the framework of WHO, EMA and US FDA biosimilar guidelines. CT-P13 has shown analytical and nonclinical features highly similar to INF including pharmacokinetics, efficacy, safety and immunogenicity profiles in ankylosing spondylitis and rheumatoid arthritis. The objective of this article is to highlight the recent biosimilar development and to review the results from the studies PLANETRA and PLANETAS, which have supported the approval of CT-P13 for several indications.
    Immunotherapy 02/2015; 7(2):73-87. DOI:10.2217/imt.14.109 · 2.44 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Globally, patents on several well established biologic agents used to treat rheumatic diseases have already or will expire over the next few years, allowing for the availability of subsequent entry biologics (SEBs or biosimilars). The objective of this study was to identify gaps in knowledge and attitudes towards SEBs among Canadian rheumatologists. Eighty-one rheumatologists completed the survey and were included in the analysis (22 % of the 369 who were contacted). We found that one third of physicians (31 %) were familiar with SEBs and that physicians with greater than 20 years of practice were significantly more likely to be familiar or very familiar with SEBs compared to respondents with less than 10 years or 10-20 years of experience (OR 11.1, 95 % CI: 2.1-55.5, p = 0.004 and OR 4.5, 95 % CI: 1.2-16.2, p = 0.023, respectively). A third (32 %) of physicians agreed or strongly agreed that they would be comfortable with indication extrapolation. Most respondents (88 %) would feel concerned or very concerned if a pharmacist had the ability to substitute a biologic drug for an SEB without the physician's approval. This survey was the first study that evaluated the position of rheumatologists on key areas surrounding SEBs from a nationwide Canadian perspective. Current physician attitudes and perceptions of SEBs can inform future educational initiatives and highlight important issues for payers, policy makers, and other stakeholders.
    Clinical Rheumatology 01/2015; DOI:10.1007/s10067-014-2835-4 · 1.77 Impact Factor

Full-text (3 Sources)

Download
16 Downloads
Available from
Jun 12, 2014