Editorial
The rise of biosimilars: potential benefits and drawbacks in rheumatoid arthritis Expert Review of Clinical Immunology Downloaded from informahealthcare.com by Nyu Medical Center on 01/11/15 For personal use only.
Expert Rev. Clin. Immunol. 10(8), 981–983 (2014)
Dae Hyun Yoo Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, College of Medicine, Seoul 133-792, Republic of Korea [email protected]
Although biologic agents are effective in the treatment of rheumatoid arthritis, the high price of drugs and restricted health care budgets have restricted easy access to biologics. Eventually, the use of biologic disease-modifying antirheumatic drugs might be inversely associated with disease activity in countries with low gross domestic product. The EMA approved an infliximab biosimilar for the first time in September 2013. The first approval of a biosimilar monoclonal antibody by a major regulatory authority provided a global standard for subsequent biosimilars and for biopharmaceutical companies developing biosimilars. Biosimilars with a highly similar quality and efficacy profile at an acceptable lower cost would significantly increase affordability of biologic disease-modifying antirheumatic drugs in the treatment of rheumatoid arthritis. Here, we will review the current status of first biosimilar antibody agent and the potential discussion points raised against biosimilars. In addition, the importance of awareness on biosimilars for stakeholders is discussed.
The introduction of biologic agents has led to a significant improvement in the treatment of rheumatoid arthritis (RA) by achieving earlier clinical improvement and showing a tendency of less radiologic progression compared to conventional disease-modifying antirheumatic drugs (DMARDs) [1]. However, the high price of drugs and restricted health care budgets are barriers to easy access to biologic DMARDs. Presumably, the annual cost for prescribing biologic DMARD for a patient ranges from US$10,000 to 25,000, depending on the price policy and health care environment [2]. Therefore, most countries have country-specific guidelines to regulate the reimbursement of biologic agents for RA treatment. Even European countries have various levels of access to biologic DMARDs, and almost 40% of Europeans living in lower-income countries have restricted access to biologic DMARDs for RA treatment. Eventually, the use of biologic DMARDs appears to be inversely associated with disease
activity in countries with low gross domestic product, compared to countries with high gross domestic product [3]. However, the patents of major biologic agents have already expired or are due to expire up by 2018 in Europe, but not in the USA. However, the patents for tocilizumab, adalimumab, rituximab and infliximab will expire in 2015, 2016, 2016 and 2018, respectively, in the USA [2,4,5]. Advances in biotechnology have also enabled developing copy versions of patent-expired originator biologics. Therefore, new biotechnology companies as well as major pharmaceutical companies are interested in the development of biosimilars. The rise of biosimilars was an important issue in rheumatology in 2013. After a positive opinion from the EMA in June 2013, the European commission approved infliximab biosimilars, Celltrion’s RemsimaTM and Hospira’s Inflectra, as the first therapeutic biosimilar monoclonal antibody in September 2013. The first approval
KEYWORDS: affordability • biosimilar • immunogenicity • infliximab • microheterogeneity • rheumatoid arthritis • switching
informahealthcare.com
10.1586/1744666X.2014.932690
Ó 2014 Informa UK Ltd
ISSN 1744-666X
981
Expert Review of Clinical Immunology Downloaded from informahealthcare.com by Nyu Medical Center on 01/11/15 For personal use only.
Editorial
Yoo
of a biosimilar monoclonal antibody by a major regulatory authority provided the global standard for subsequent biosimilars and for biopharmaceutical companies developing biosimilars [4,6]. The development of biosimilar agents includes stringent comparability exercises to prove that the biosimilar candidate and the reference agent are highly similar in their physiochemical, biological, preclinical and clinical aspects. Microheterogeneity is a normal feature of biological agents, both originator and biosimilar [4,6]. To demonstrate that the biosimilar and its reference product are comparable in all relevant functional and structural aspects, applicants have to submit extensive evidence derived from currently available methodologies including mass spectrometry [7,8]. The actual approval process for a biosimilar is very critical and stringent, and no step in this process is accepted without scientific assessment by regulatory authorities. The timeline for the biosimilar review process by the EMA is as long as that of the previously approved innovator biologic agents [4]. The time to positive opinion on CTP-13 issued by the EMA was almost 500 days including clock stop periods (personal communication with Celltrion). The biosimilar to infliximab, CTP-13, was studied in RA and ankylosing spondylitis patients, and clinical studies have demonstrated that CTP-13 has equivalent pharmacokinetics and efficacy as well as comparable safety profiles to those of the innovator infliximab [9–11]. A true biosimilar agent, approved by the EMA or the US FDA, could be regarded as trustworthy and must be differentiated from the so-called me-too biologics or intended copies, which are on the market in some countries without stringent comparability exercises [2,4]. The concerns currently raised against biosimilar products are their efficacy, safety profile including immunogenicity, indication extrapolation, interchangeability, long-term effects and naming [2,4,11–15]. Among the many safety issues, there is a major concern whether immunogenicity may affect the adverse events, infusion or injection site reaction, hypersensitivity, pharmacokinetic profile, pharmacodynamic profiles or clinical efficacy [12]. Recent data have shown that there has been no further increase in the antidrug antibody positive rate after 6 months of treatment, and that the positive rate was comparable between CTP-13 and the reference agent [11,13]. Indication extrapolation was raised by originator companies and physicians of other specialties [14]. However, the issue could be solved by some noninferiority clinical studies, which would increase confidence in biosimilars by physicians, patients and the other stakeholders. Concerning switching and interchangeability, the most important questions about switching are loss of efficacy or emergence of a hypersensitivity reaction after switching, although evidence is still lacking [15]. Switching from the originator infliximab to infliximab biosimilar CTP-13 showed maintenance of efficacy and comparable safety for 1 year [11,13]. Instead of repeating large clinical studies, strict post-marketing surveys or pharmacovigilance studies with a registry in all approved indications are required to guarantee long-term efficacy, safety including immunogenicity and switching/interchangeability of each biosimilar agent. These activities are also recommended by regulatory 982
authorities including the EMA. All these activities can support confidence in biosimilar monoclonal antibody or fusion protein in the rheumatic disease field. Also, all those findings must be listed in the summary of product characteristics for further reference. When biologic agents with highly similar quality and efficacy profile at a lower cost are available, the affordability of biologic DMARDs would significantly improve in the treatment of RA. Although lower cost is a major advantage of biosimilar agents, cost must not override safety and efficacy. However, the cost of a biosimilar agent is the most important factor for penetration in the market, and pharmacoeconomic analysis is required to clarify how lower a price is really cost effective. According to scenarios of starting biosimilar infliximab for new cases only, or switching originator to biosimilar infliximab in 80%, the use of biosimilar infliximab enabled that 1200–1800 more patients could be treated with biologic agents in six Eastern and Central European countries for 3 years if the price of biosimilar is 25% less than that of the reference infliximab [16]. Recently, some comparative effectiveness studies [17,18] have demonstrated that biologic agents are superior to conventional combination therapy in terms of radiologic progression, but not in clinical outcome measures at 2 years. The current treatment recommendation for RA does not support early biologic therapy being cost effective at the present price [19]. When biosimilar agents are affordable at an acceptable cost, earlier use of biosimilar agents could have better cost–effectiveness than the originators in the treatment of active RA patients with poor prognosis factors. The first infliximab biosimilar was approved in 46 countries and is currently on the market in 34 countries including South Korea, the Philippines, some South American countries and Canada. Although infliximab biosimilar has been approved by most countries in Europe and is already on the market in many European countries, launching has been postponed in 12 European countries until February 2015 due to an extension of the originator infliximab’s patent (20 and personal communication with Celltrion). Recently, the Norwegian government invited bids for therapeutic biologic agents for new-onset patients with approved indications, and accepted Remsima at a price 39% less than that of the originator. Norwegian physicians are planning clinical studies to look at the efficacy and safety of switching from the originator to the infliximab biosimilar [20]. The lower annual cost for treatment with the biosimilar infliximab may increase access to biologic therapy and decrease the financial burden on society [20]. If additional biosimilar agents are available in a few years, the cost of biologic treatment would be further reduced. Practically, the prescribing physicians play the most important role in the penetration of biosimilars in rheumatic diseases, and the critical point is the confidence in biosimilars by working rheumatologists. A recent survey of 470 European physicians belonging to various specialties including rheumatology, nephrology, oncology and dermatology from five European Expert Rev. Clin. Immunol. 10(8), (2014)
Expert Review of Clinical Immunology Downloaded from informahealthcare.com by Nyu Medical Center on 01/11/15 For personal use only.
The rise of biosimilars
countries (France, Germany, Italy, Spain and the UK) showed insufficient understanding of biosimilar. Only 22% responded that they were very familiar with biosimilars, and could define what it is. While a majority (54%) had a basic understanding of biosimilars, 24% of them answered that they had never heard of biosimilar before [21]. Due to insufficient understanding of biosimilars, half of them thought that biosimilars have to use different International Non-proprietary Names from the originator biologic agents. However, this understanding of International Non-proprietary Name is misleading and is definitely different from regulatory authorities [22]. Providing information on biosimilars to medical doctors, pharmacists, nurses, patients and health care funders is important to promote penetration of biosimilars in treatment. With
1.
2.
3.
Nam JL, Ramiro S, Gaujoux-Viala C, et al. Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis. Rheum Dis 2014;73:516-28
4.
Schneider CK. Biosimilars in rheumatology: the wind of change. Ann Rheum Dis 2013;72:315-18
5.
Scheinberg MA, Kay J. The advent of biosimilar therapies in rheumatology—“O Brave New World”. Nat Rev Rheumatol 2012;8:430-6
6.
Beck A, Reichert JM. Approval of the first biosimilar antibodies in Europe: a major landmark for the biopharmaceutical industry. MAbs 2013;5:621-3
7.
Beck A, Wagner-Rousset E, Ayoub D, et al. Characterization of therapeutic antibodies and related products. Anal Chem 2013;85: 715-36
8.
9.
10.
Do¨rner T, Strand V, Castan˜eda-Herna´ndez G, et al. The role of biosimilars in the treatment of rheumatic diseases. Ann Rheum Dis 2013;72:322-8 Putrik P, Ramiro S, Kvien TK, et al. Inequities in access to biologic and synthetic DMARDs across 46 European countries. Ann Rheum Dis 2014;73:198-206
Beck A, Diemer H, Ayoub D, et al. Analytical characterization of biosimilar antibodies and Fc-fusion proteins. Trends Anal Chem 2013;48:81-95 Yoo DH, Hrycaj P, Miranda P, et al. A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with
informahealthcare.com
improvement of awareness, doctors, patients and the other stakeholders can discuss to select the most suitable biological agent based on a patient’s needs. With the advent of biosimilar agents in the treatment of immune-mediated inflammatory diseases, researches on next-generation biologic agents, called biobetters, can emerge as a new area of innovation. Financial & competing interests disclosure
DH Yoo is a scientific consultant of Celltrion. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.
innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Ann Rheum Dis 2013;72:1613-20
References
Park W, Hrycaj P, Jeka S, et al. A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study. Ann Rheum Dis 2013;72:1605-12
11.
McKeage K. A review of CT P-13: infliximab biosimilar. BioDrugs 2014;28: 313-21
12.
Maneiro JR, Salgado E, Gomez-Reino JJ. Immunogenicity of monoclonal antibodies against tumor necrosis factor used in chronic immune-mediated inflammatory conditions. systematic review and meta-analysis. JAMA Intern Med 2013;173: 1416-28
13.
14.
15.
16.
Editorial
Yoo DH. Efficacy and safety of CT-P13 (Infliximab biosimilar) over two years in patients with rheumatoid arthritis: comparison between continued CT-P13 and switching from Infliximab to CT-P13 (abstract no L1). ACR annual meeting; San Diego, CA, USA; 2013 Gecse KB, Khanna R, van den Brink GR, et al. Biosimilars in IBD: hope or expectation? Gut 2013;62:803-7 Ebbers HC, Muenzberg M, Schellekens H. The safety of switching between therapeutic proteins. Expert Opin Biol Ther 2012;12: 1473-85
rheumatoid arthritis in six Central and Eastern European countries. Eur J Health Econ 2014;15(Suppl 1):65-71 17.
Moreland LW, O’Dell JR, Paulus HE, et al. A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: the treatment of early aggressive rheumatoid arthritis trial. Arthritis Rheum 2012;64:2824-35
18.
Vollenhoven RFV, Geborek P, Forslind K, et al. Conventional combination treatment versus biological treatment in methotrexate-refractory early rheumatoid arthritis: 2 year follow-up of the randomised, non-blinded, parallel-group Swefot trial. Lancet 2012;379:1712-20
19.
Schoels M, Wong J, Scott DL, et al. Economic aspects of treatment options in rheumatoid arthritis: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 2010;69:996-1004
20.
Norway’s discount on infliximab: a litmus test for biosimilar expansion in Europe? Available from: http://healthcare.blogs.ihs. com/2014/03/20/norways-discount-oninfliximab-a-litmus-test-for-biosimilarexpansion-in-europe/
21.
Biosimilar companies has marketing problem. Biosimilar news. 2014. Available from: www.biosimilarnews.com/tags/asbm
22.
Editorial. The INN crowd. Nat Biotechnol 2013;31:1055
Brodszky V, Baji P, Balogh O, Pe´ntek M. Budget impact analysis of biosimilar infliximab (CT-P13) for the treatment of
983
The rise of biosimilars: potential benefits and drawbacks in rheumatoid arthritis Expert Review of Clinical Immunology Downloaded from informahealthcare.com by Nyu Medical Center on 01/11/15 For personal use only.
Expert Rev. Clin. Immunol. 10(8), 981–983 (2014)
Dae Hyun Yoo Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, College of Medicine, Seoul 133-792, Republic of Korea [email protected]
Although biologic agents are effective in the treatment of rheumatoid arthritis, the high price of drugs and restricted health care budgets have restricted easy access to biologics. Eventually, the use of biologic disease-modifying antirheumatic drugs might be inversely associated with disease activity in countries with low gross domestic product. The EMA approved an infliximab biosimilar for the first time in September 2013. The first approval of a biosimilar monoclonal antibody by a major regulatory authority provided a global standard for subsequent biosimilars and for biopharmaceutical companies developing biosimilars. Biosimilars with a highly similar quality and efficacy profile at an acceptable lower cost would significantly increase affordability of biologic disease-modifying antirheumatic drugs in the treatment of rheumatoid arthritis. Here, we will review the current status of first biosimilar antibody agent and the potential discussion points raised against biosimilars. In addition, the importance of awareness on biosimilars for stakeholders is discussed.
The introduction of biologic agents has led to a significant improvement in the treatment of rheumatoid arthritis (RA) by achieving earlier clinical improvement and showing a tendency of less radiologic progression compared to conventional disease-modifying antirheumatic drugs (DMARDs) [1]. However, the high price of drugs and restricted health care budgets are barriers to easy access to biologic DMARDs. Presumably, the annual cost for prescribing biologic DMARD for a patient ranges from US$10,000 to 25,000, depending on the price policy and health care environment [2]. Therefore, most countries have country-specific guidelines to regulate the reimbursement of biologic agents for RA treatment. Even European countries have various levels of access to biologic DMARDs, and almost 40% of Europeans living in lower-income countries have restricted access to biologic DMARDs for RA treatment. Eventually, the use of biologic DMARDs appears to be inversely associated with disease
activity in countries with low gross domestic product, compared to countries with high gross domestic product [3]. However, the patents of major biologic agents have already expired or are due to expire up by 2018 in Europe, but not in the USA. However, the patents for tocilizumab, adalimumab, rituximab and infliximab will expire in 2015, 2016, 2016 and 2018, respectively, in the USA [2,4,5]. Advances in biotechnology have also enabled developing copy versions of patent-expired originator biologics. Therefore, new biotechnology companies as well as major pharmaceutical companies are interested in the development of biosimilars. The rise of biosimilars was an important issue in rheumatology in 2013. After a positive opinion from the EMA in June 2013, the European commission approved infliximab biosimilars, Celltrion’s RemsimaTM and Hospira’s Inflectra, as the first therapeutic biosimilar monoclonal antibody in September 2013. The first approval
KEYWORDS: affordability • biosimilar • immunogenicity • infliximab • microheterogeneity • rheumatoid arthritis • switching
informahealthcare.com
10.1586/1744666X.2014.932690
Ó 2014 Informa UK Ltd
ISSN 1744-666X
981
Expert Review of Clinical Immunology Downloaded from informahealthcare.com by Nyu Medical Center on 01/11/15 For personal use only.
Editorial
Yoo
of a biosimilar monoclonal antibody by a major regulatory authority provided the global standard for subsequent biosimilars and for biopharmaceutical companies developing biosimilars [4,6]. The development of biosimilar agents includes stringent comparability exercises to prove that the biosimilar candidate and the reference agent are highly similar in their physiochemical, biological, preclinical and clinical aspects. Microheterogeneity is a normal feature of biological agents, both originator and biosimilar [4,6]. To demonstrate that the biosimilar and its reference product are comparable in all relevant functional and structural aspects, applicants have to submit extensive evidence derived from currently available methodologies including mass spectrometry [7,8]. The actual approval process for a biosimilar is very critical and stringent, and no step in this process is accepted without scientific assessment by regulatory authorities. The timeline for the biosimilar review process by the EMA is as long as that of the previously approved innovator biologic agents [4]. The time to positive opinion on CTP-13 issued by the EMA was almost 500 days including clock stop periods (personal communication with Celltrion). The biosimilar to infliximab, CTP-13, was studied in RA and ankylosing spondylitis patients, and clinical studies have demonstrated that CTP-13 has equivalent pharmacokinetics and efficacy as well as comparable safety profiles to those of the innovator infliximab [9–11]. A true biosimilar agent, approved by the EMA or the US FDA, could be regarded as trustworthy and must be differentiated from the so-called me-too biologics or intended copies, which are on the market in some countries without stringent comparability exercises [2,4]. The concerns currently raised against biosimilar products are their efficacy, safety profile including immunogenicity, indication extrapolation, interchangeability, long-term effects and naming [2,4,11–15]. Among the many safety issues, there is a major concern whether immunogenicity may affect the adverse events, infusion or injection site reaction, hypersensitivity, pharmacokinetic profile, pharmacodynamic profiles or clinical efficacy [12]. Recent data have shown that there has been no further increase in the antidrug antibody positive rate after 6 months of treatment, and that the positive rate was comparable between CTP-13 and the reference agent [11,13]. Indication extrapolation was raised by originator companies and physicians of other specialties [14]. However, the issue could be solved by some noninferiority clinical studies, which would increase confidence in biosimilars by physicians, patients and the other stakeholders. Concerning switching and interchangeability, the most important questions about switching are loss of efficacy or emergence of a hypersensitivity reaction after switching, although evidence is still lacking [15]. Switching from the originator infliximab to infliximab biosimilar CTP-13 showed maintenance of efficacy and comparable safety for 1 year [11,13]. Instead of repeating large clinical studies, strict post-marketing surveys or pharmacovigilance studies with a registry in all approved indications are required to guarantee long-term efficacy, safety including immunogenicity and switching/interchangeability of each biosimilar agent. These activities are also recommended by regulatory 982
authorities including the EMA. All these activities can support confidence in biosimilar monoclonal antibody or fusion protein in the rheumatic disease field. Also, all those findings must be listed in the summary of product characteristics for further reference. When biologic agents with highly similar quality and efficacy profile at a lower cost are available, the affordability of biologic DMARDs would significantly improve in the treatment of RA. Although lower cost is a major advantage of biosimilar agents, cost must not override safety and efficacy. However, the cost of a biosimilar agent is the most important factor for penetration in the market, and pharmacoeconomic analysis is required to clarify how lower a price is really cost effective. According to scenarios of starting biosimilar infliximab for new cases only, or switching originator to biosimilar infliximab in 80%, the use of biosimilar infliximab enabled that 1200–1800 more patients could be treated with biologic agents in six Eastern and Central European countries for 3 years if the price of biosimilar is 25% less than that of the reference infliximab [16]. Recently, some comparative effectiveness studies [17,18] have demonstrated that biologic agents are superior to conventional combination therapy in terms of radiologic progression, but not in clinical outcome measures at 2 years. The current treatment recommendation for RA does not support early biologic therapy being cost effective at the present price [19]. When biosimilar agents are affordable at an acceptable cost, earlier use of biosimilar agents could have better cost–effectiveness than the originators in the treatment of active RA patients with poor prognosis factors. The first infliximab biosimilar was approved in 46 countries and is currently on the market in 34 countries including South Korea, the Philippines, some South American countries and Canada. Although infliximab biosimilar has been approved by most countries in Europe and is already on the market in many European countries, launching has been postponed in 12 European countries until February 2015 due to an extension of the originator infliximab’s patent (20 and personal communication with Celltrion). Recently, the Norwegian government invited bids for therapeutic biologic agents for new-onset patients with approved indications, and accepted Remsima at a price 39% less than that of the originator. Norwegian physicians are planning clinical studies to look at the efficacy and safety of switching from the originator to the infliximab biosimilar [20]. The lower annual cost for treatment with the biosimilar infliximab may increase access to biologic therapy and decrease the financial burden on society [20]. If additional biosimilar agents are available in a few years, the cost of biologic treatment would be further reduced. Practically, the prescribing physicians play the most important role in the penetration of biosimilars in rheumatic diseases, and the critical point is the confidence in biosimilars by working rheumatologists. A recent survey of 470 European physicians belonging to various specialties including rheumatology, nephrology, oncology and dermatology from five European Expert Rev. Clin. Immunol. 10(8), (2014)
Expert Review of Clinical Immunology Downloaded from informahealthcare.com by Nyu Medical Center on 01/11/15 For personal use only.
The rise of biosimilars
countries (France, Germany, Italy, Spain and the UK) showed insufficient understanding of biosimilar. Only 22% responded that they were very familiar with biosimilars, and could define what it is. While a majority (54%) had a basic understanding of biosimilars, 24% of them answered that they had never heard of biosimilar before [21]. Due to insufficient understanding of biosimilars, half of them thought that biosimilars have to use different International Non-proprietary Names from the originator biologic agents. However, this understanding of International Non-proprietary Name is misleading and is definitely different from regulatory authorities [22]. Providing information on biosimilars to medical doctors, pharmacists, nurses, patients and health care funders is important to promote penetration of biosimilars in treatment. With
1.
2.
3.
Nam JL, Ramiro S, Gaujoux-Viala C, et al. Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis. Rheum Dis 2014;73:516-28
4.
Schneider CK. Biosimilars in rheumatology: the wind of change. Ann Rheum Dis 2013;72:315-18
5.
Scheinberg MA, Kay J. The advent of biosimilar therapies in rheumatology—“O Brave New World”. Nat Rev Rheumatol 2012;8:430-6
6.
Beck A, Reichert JM. Approval of the first biosimilar antibodies in Europe: a major landmark for the biopharmaceutical industry. MAbs 2013;5:621-3
7.
Beck A, Wagner-Rousset E, Ayoub D, et al. Characterization of therapeutic antibodies and related products. Anal Chem 2013;85: 715-36
8.
9.
10.
Do¨rner T, Strand V, Castan˜eda-Herna´ndez G, et al. The role of biosimilars in the treatment of rheumatic diseases. Ann Rheum Dis 2013;72:322-8 Putrik P, Ramiro S, Kvien TK, et al. Inequities in access to biologic and synthetic DMARDs across 46 European countries. Ann Rheum Dis 2014;73:198-206
Beck A, Diemer H, Ayoub D, et al. Analytical characterization of biosimilar antibodies and Fc-fusion proteins. Trends Anal Chem 2013;48:81-95 Yoo DH, Hrycaj P, Miranda P, et al. A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with
informahealthcare.com
improvement of awareness, doctors, patients and the other stakeholders can discuss to select the most suitable biological agent based on a patient’s needs. With the advent of biosimilar agents in the treatment of immune-mediated inflammatory diseases, researches on next-generation biologic agents, called biobetters, can emerge as a new area of innovation. Financial & competing interests disclosure
DH Yoo is a scientific consultant of Celltrion. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.
innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Ann Rheum Dis 2013;72:1613-20
References
Park W, Hrycaj P, Jeka S, et al. A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study. Ann Rheum Dis 2013;72:1605-12
11.
McKeage K. A review of CT P-13: infliximab biosimilar. BioDrugs 2014;28: 313-21
12.
Maneiro JR, Salgado E, Gomez-Reino JJ. Immunogenicity of monoclonal antibodies against tumor necrosis factor used in chronic immune-mediated inflammatory conditions. systematic review and meta-analysis. JAMA Intern Med 2013;173: 1416-28
13.
14.
15.
16.
Editorial
Yoo DH. Efficacy and safety of CT-P13 (Infliximab biosimilar) over two years in patients with rheumatoid arthritis: comparison between continued CT-P13 and switching from Infliximab to CT-P13 (abstract no L1). ACR annual meeting; San Diego, CA, USA; 2013 Gecse KB, Khanna R, van den Brink GR, et al. Biosimilars in IBD: hope or expectation? Gut 2013;62:803-7 Ebbers HC, Muenzberg M, Schellekens H. The safety of switching between therapeutic proteins. Expert Opin Biol Ther 2012;12: 1473-85
rheumatoid arthritis in six Central and Eastern European countries. Eur J Health Econ 2014;15(Suppl 1):65-71 17.
Moreland LW, O’Dell JR, Paulus HE, et al. A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: the treatment of early aggressive rheumatoid arthritis trial. Arthritis Rheum 2012;64:2824-35
18.
Vollenhoven RFV, Geborek P, Forslind K, et al. Conventional combination treatment versus biological treatment in methotrexate-refractory early rheumatoid arthritis: 2 year follow-up of the randomised, non-blinded, parallel-group Swefot trial. Lancet 2012;379:1712-20
19.
Schoels M, Wong J, Scott DL, et al. Economic aspects of treatment options in rheumatoid arthritis: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 2010;69:996-1004
20.
Norway’s discount on infliximab: a litmus test for biosimilar expansion in Europe? Available from: http://healthcare.blogs.ihs. com/2014/03/20/norways-discount-oninfliximab-a-litmus-test-for-biosimilarexpansion-in-europe/
21.
Biosimilar companies has marketing problem. Biosimilar news. 2014. Available from: www.biosimilarnews.com/tags/asbm
22.
Editorial. The INN crowd. Nat Biotechnol 2013;31:1055
Brodszky V, Baji P, Balogh O, Pe´ntek M. Budget impact analysis of biosimilar infliximab (CT-P13) for the treatment of
983
