[Pegylation and interferons in multiple sclerosis]
DOI:
https://doi.org/10.7175/fe.v17i2S.1229Keywords:
PEG, Interferon beta-1a, Plegridy, Half-lifeAbstract
Pegylation is a procedure used for drug development since the 1970s and consists of the conjugation of a polyethylene glycol molecule (PEG) to a drug. PEG has shown to be safe and effective in improving the pharmacokinetic and pharmacodynamic profile of drugs. Recently, a 20 kDa linear chain of PEG was conjugated to interferon beta-1a with the aim to offer a new treatment option to relapsing-remitting multiple sclerosis (RRMS) patients. Due to a prolonged bioavailability, this new drug can be administered less frequently (every two weeks) than the other interferons beta available, thus allowing to hypothesize a better adherence to the treatment, which, in turn, should result in better clinical and economic outcomes. A phase III clinical trial has proven its effectiveness compared to placebo in RRMS patients, as well as a safety profile comparable to that found in other interferon beta preparations. The immunogenicity of this new molecule is < 1%, thus minimizing the suppression or reduction of interferon beta biological activity that could come from the development of Neutralizing Antibodies (NAbs).
[Article in Italian]
References
Webster R, Didier E, Harris P, et al. PEGylated proteins: evaluation of their safety in the absence of definitive metabolism studies. Drug Metab Dispos 2007; 35: 9-16; http://dx.doi.org/10.1124/dmd.106.012419
Harris JM, Chess RB. Effect of pegylation on pharmaceuticals. Nat Rev Drug Discov 2003; 2: 214-21; http://dx.doi.org/10.1038/nrd1033
Davis FF, Abuchowski A, van Es T, et al. Polyethylene Glycol adducts: modified enzymes with unique properties. Enzyme Eng 1978; 4: 169-73; http://dx.doi.org/10.1007/978-1-4684-6985-1_35
Howley A, Kremenchutzky M. Pegylated interferons: a nurses’ review of a novel multiple sclerosis therapy. J Neurosci Nurs 2014; 46: 88-96; http://dx.doi.org/10.1097/JNN.0000000000000039
Kieseier BC, Calabresi PA. PEGylation of interferon-beta-1a: a promising strategy in multiple sclerosis. CNS Drugs 2012; 26: 205-14; http://dx.doi.org/10.2165/11596970-000000000-00000
Lindsay KL, Trepo C, Heintges T, et al; Hepatitis Interventional Therapy Group. A randomized, double-blind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C. Hepatology 2001; 34: 395-403; http://dx.doi.org/10.1053/jhep.2001.26371
Zeuzem S, Feinman SV, Rasenack J, et al. Peginterferon alfa-2a in patients with chronic hepatitis C. N Engl J Med 2000; 343: 1666-72; http://dx.doi.org/10.1056/NEJM200012073432301
Holmes FA, Jones SE, O’Shaughnessy J, et al. Comparable efficacy and safety profiles of once-per-cycle pegfilgrastim and daily injection filgrastim in chemotherapy-induced neutropenia: a multicenter dose-finding study in women with breast cancer. Ann Oncol 2002; 13: 903-9; http://dx.doi.org/10.1093/annonc/mdf130
Levin NW, Fishbane S, Ca-edo FV, et al; MAXIMA study investigators. Intravenous methoxy polyethylene glycol-epoetin beta for haemoglobin control in patients with chronic kidney disease who are on dialysis: a randomised non-inferiority trial (MAXIMA). Lancet 2007; 370: 1415-21; http://dx.doi.org/10.1016/S0140-6736(07)61599-2
Food and Drug Administration. FDA approved drugs products. Diponibile all’indirizzo http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm (ultimo accesso maggio 2015)
European Medicines Agency. European public assessment reports. Disponibile all’indirizzo http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/landing/epar_search.jsp&mid=WC0b01ac058001d124 (ultimo accesso maggio 2015)
Baker DP, Pepinsky RB, Brickelmaier M, et al. PEGylated interferon beta-1a: meeting an unmet medical need in the treatment of relapsing multiple sclerosis. J Interferon Cytokine Res 2010; 30: 777-85; http://dx.doi.org/10.1089/jir.2010.0092
Baker DP, Lin EY, Lin K, et al. N-terminally PEGylated human interferon-beta-1a with improved pharmacokinetic properties and in vivo efficacy in a melanoma angiogenesis model. Bioconjug Chem 2006; 17: 179-88; http://dx.doi.org/10.1021/bc050237q
Plegridy [summary or product characteristics]. Cambridge, MA: Biogen Idec; 2014
Hoy SM. Peginterferon Beta-1a: a review of its use in patients with relapsing-remitting multiple sclerosis. CNS Drugs 2015; 29: 171-9; http://dx.doi.org/10.1007/s40263-015-0227-1
Ivanova JI, Bergman RE, Birnbaum HG, et al. Impact of medication adherence to disease-modifying drugs on severe relapse, and direct and indirect costs among employees with multiple sclerosis in the US. J Med Econ 2012; 15: 601-9; http://dx.doi.org/10.3111/13696998.2012.667027
Calabresi PA, Kieseier BC, Arnold DL, et al; ADVANCE Study Investigators. Pegylated interferon β-1a for relapsing-remitting multiple sclerosis (ADVANCE): a randomised, phase 3, double-blind study. Lancet Neurol 2014; 13: 657-65; http://dx.doi.org/10.1016/S1474-4422(14)70068-7
Kieseier BC, Arnold DL, Balcer LJ, et al. Peginterferon beta-1a in multiple sclerosis: 2-year results from ADVANCE. Mult Scler 2015; 21: 1025-35; http://dx.doi.org/10.1177/1352458514557986
Committee for Medicinal Products for Human Use (CHMP). EMA/339024/2014. Plegridy: assessment report. International non-proprietary name: peginterferon beta-1a. Procedure No. EMEA/H/C/002827/0000. 22 May 2014. Disponibile all’indirizzo: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002827/WC500170303.pdf (ultimo accesso maggio 2015)
Bertolotto A, Capobianco M, Amato MP, et al; Italian Multiple Sclerosis Study group. Guidelines on the clinical use for the detection of neutralizing antibodies (NAbs) to IFN beta in multiple sclerosis therapy: report from the Italian Multiple Sclerosis Study group. Neurol Sci 2014; 35: 307-16; http://dx.doi.org/10.1007/s10072-013-1616-1
Paolicelli D, D’Onghia M, Pellegrini F, et al. The impact of neutralizing antibodies on the risk of disease worsening in interferon β-treated relapsing multiple sclerosis: a 5 year post-marketing study. J Neurol 2013; 260: 1562-8; http://dx.doi.org/10.1007/s00415-012-6829-3
Kobelt G, Berg J, Lindgren P, et al. Costs and quality of life of multiple sclerosis in Italy. Eur J Health Econ. 2006; 7 Suppl 2: S45-54; http://dx.doi.org/10.1007/s10198-006-0385-7
Published
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal. The Publication Agreement can be downloaded here, and should be signed by the Authors and sent to the Publisher when the article has been accepted for publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (see The Effect of Open Access).
- Authors are permitted to post their work online after publication (the article must link to publisher version, in html format)