@article{link_clinical_2017,
	title = {Clinical practice of analysis of anti-drug antibodies against interferon beta and natalizumab in multiple sclerosis patients in {Europe}: {A} descriptive study of test results},
	volume = {12},
	issn = {1932-6203},
	shorttitle = {Clinical practice of analysis of anti-drug antibodies against interferon beta and natalizumab in multiple sclerosis patients in {Europe}},
	doi = {10.1371/journal.pone.0170395},
	abstract = {Antibodies against biopharmaceuticals (anti-drug antibodies, ADA) have been a well-integrated part of the clinical care of multiple sclerosis (MS) in several European countries. ADA data generated in Europe during the more than 10 years of ADA monitoring in MS patients treated with interferon beta (IFNβ) and natalizumab have been pooled and characterized through collaboration within a European consortium. The aim of this study was to report on the clinical practice of ADA testing in Europe, considering the number of ADA tests performed and type of ADA assays used, and to determine the frequency of ADA testing against the different drug preparations in different countries. A common database platform (tranSMART) for querying, analyzing and storing retrospective data of MS cohorts was set up to harmonize the data and compare results of ADA tests between different countries. Retrospective data from six countries (Sweden, Austria, Spain, Switzerland, Germany and Denmark) on 20,695 patients and on 42,555 samples were loaded into tranSMART including data points of age, gender, treatment, samples, and ADA results. The previously observed immunogenic difference among the four IFNβ preparations was confirmed in this large dataset. Decreased usage of the more immunogenic preparations IFNβ-1a subcutaneous (s.c.) and IFNβ-1b s.c. in favor of the least immunogenic preparation IFNβ-1a intramuscular (i.m.) was observed. The median time from treatment start to first ADA test correlated with time to first positive test. Shorter times were observed for IFNβ-1b-Extavia s.c. (0.99 and 0.94 years) and natalizumab (0.25 and 0.23 years), which were introduced on the market when ADA testing was already available, as compared to IFNβ-1a i.m. (1.41 and 2.27 years), IFNβ-1b-Betaferon s.c. (2.51 and 1.96 years) and IFNβ-1a s.c. (2.11 and 2.09 years) which were available years before routine testing began. A higher rate of anti-IFNβ ADA was observed in test samples taken from older patients. Testing for ADA varies between different European countries and is highly dependent on the policy within each country. For drugs where routine monitoring of ADA is not in place, there is a risk that some patients remain on treatment for several years despite ADA positivity. For drugs where a strategy of ADA testing is introduced with the release of the drug, there is a reduced risk of having ADA positive patients and thus of less efficient treatment. This indicates that potential savings in health cost might be achieved by routine analysis of ADA.},
	language = {eng},
	number = {2},
	journal = {PloS One},
	author = {Link, Jenny and Ramanujam, Ryan and Auer, Michael and Ryner, Malin and Hässler, Signe and Bachelet, Delphine and Mbogning, Cyprien and Warnke, Clemens and Buck, Dorothea and Hyldgaard Jensen, Poul Erik and Sievers, Claudia and Ingenhoven, Kathleen and Fissolo, Nicolas and Lindberg, Raija and Grummel, Verena and Donnellan, Naoimh and Comabella, Manuel and Montalban, Xavier and Kieseier, Bernd and Soelberg Sørensen, Per and Hartung, Hans-Peter and Derfuss, Tobias and Lawton, Andy and Sikkema, Dan and Pallardy, Marc and Hemmer, Bernhard and Deisenhammer, Florian and Broët, Philippe and Dönnes, Pierre and Davidson, Julie and Fogdell-Hahn, Anna and {ABIRISK Consortium}},
	year = {2017},
	pmid = {28170401},
	pmcid = {PMC5295710},
	keywords = {Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Antibodies, Child, Child, Preschool, Europe, Female, Humans, Immunologic Factors, Infant, Infant, Newborn, Interferon-beta, Male, Middle Aged, Multiple Sclerosis, Natalizumab, Retrospective Studies, Sex Factors, Time Factors, Young Adult},
	pages = {e0170395},
}

{"_id":"kQd8pR7ArorENDxDB","bibbaseid":"link-ramanujam-auer-ryner-hssler-bachelet-mbogning-warnke-etal-clinicalpracticeofanalysisofantidrugantibodiesagainstinterferonbetaandnatalizumabinmultiplesclerosispatientsineuropeadescriptivestudyoftestresults-2017","authorIDs":[],"author_short":["Link, J.","Ramanujam, R.","Auer, M.","Ryner, M.","Hässler, S.","Bachelet, D.","Mbogning, C.","Warnke, C.","Buck, D.","Hyldgaard Jensen, P. E.","Sievers, C.","Ingenhoven, K.","Fissolo, N.","Lindberg, R.","Grummel, V.","Donnellan, N.","Comabella, M.","Montalban, X.","Kieseier, B.","Soelberg Sørensen, P.","Hartung, H.","Derfuss, T.","Lawton, A.","Sikkema, D.","Pallardy, M.","Hemmer, B.","Deisenhammer, F.","Broët, P.","Dönnes, P.","Davidson, J.","Fogdell-Hahn, A.","ABIRISK Consortium"],"bibdata":{"bibtype":"article","type":"article","title":"Clinical practice of analysis of anti-drug antibodies against interferon beta and natalizumab in multiple sclerosis patients in Europe: A descriptive study of test results","volume":"12","issn":"1932-6203","shorttitle":"Clinical practice of analysis of anti-drug antibodies against interferon beta and natalizumab in multiple sclerosis patients in Europe","doi":"10.1371/journal.pone.0170395","abstract":"Antibodies against biopharmaceuticals (anti-drug antibodies, ADA) have been a well-integrated part of the clinical care of multiple sclerosis (MS) in several European countries. ADA data generated in Europe during the more than 10 years of ADA monitoring in MS patients treated with interferon beta (IFNβ) and natalizumab have been pooled and characterized through collaboration within a European consortium. The aim of this study was to report on the clinical practice of ADA testing in Europe, considering the number of ADA tests performed and type of ADA assays used, and to determine the frequency of ADA testing against the different drug preparations in different countries. A common database platform (tranSMART) for querying, analyzing and storing retrospective data of MS cohorts was set up to harmonize the data and compare results of ADA tests between different countries. Retrospective data from six countries (Sweden, Austria, Spain, Switzerland, Germany and Denmark) on 20,695 patients and on 42,555 samples were loaded into tranSMART including data points of age, gender, treatment, samples, and ADA results. The previously observed immunogenic difference among the four IFNβ preparations was confirmed in this large dataset. Decreased usage of the more immunogenic preparations IFNβ-1a subcutaneous (s.c.) and IFNβ-1b s.c. in favor of the least immunogenic preparation IFNβ-1a intramuscular (i.m.) was observed. The median time from treatment start to first ADA test correlated with time to first positive test. Shorter times were observed for IFNβ-1b-Extavia s.c. (0.99 and 0.94 years) and natalizumab (0.25 and 0.23 years), which were introduced on the market when ADA testing was already available, as compared to IFNβ-1a i.m. (1.41 and 2.27 years), IFNβ-1b-Betaferon s.c. (2.51 and 1.96 years) and IFNβ-1a s.c. (2.11 and 2.09 years) which were available years before routine testing began. A higher rate of anti-IFNβ ADA was observed in test samples taken from older patients. Testing for ADA varies between different European countries and is highly dependent on the policy within each country. For drugs where routine monitoring of ADA is not in place, there is a risk that some patients remain on treatment for several years despite ADA positivity. For drugs where a strategy of ADA testing is introduced with the release of the drug, there is a reduced risk of having ADA positive patients and thus of less efficient treatment. This indicates that potential savings in health cost might be achieved by routine analysis of ADA.","language":"eng","number":"2","journal":"PloS One","author":[{"propositions":[],"lastnames":["Link"],"firstnames":["Jenny"],"suffixes":[]},{"propositions":[],"lastnames":["Ramanujam"],"firstnames":["Ryan"],"suffixes":[]},{"propositions":[],"lastnames":["Auer"],"firstnames":["Michael"],"suffixes":[]},{"propositions":[],"lastnames":["Ryner"],"firstnames":["Malin"],"suffixes":[]},{"propositions":[],"lastnames":["Hässler"],"firstnames":["Signe"],"suffixes":[]},{"propositions":[],"lastnames":["Bachelet"],"firstnames":["Delphine"],"suffixes":[]},{"propositions":[],"lastnames":["Mbogning"],"firstnames":["Cyprien"],"suffixes":[]},{"propositions":[],"lastnames":["Warnke"],"firstnames":["Clemens"],"suffixes":[]},{"propositions":[],"lastnames":["Buck"],"firstnames":["Dorothea"],"suffixes":[]},{"propositions":[],"lastnames":["Hyldgaard","Jensen"],"firstnames":["Poul","Erik"],"suffixes":[]},{"propositions":[],"lastnames":["Sievers"],"firstnames":["Claudia"],"suffixes":[]},{"propositions":[],"lastnames":["Ingenhoven"],"firstnames":["Kathleen"],"suffixes":[]},{"propositions":[],"lastnames":["Fissolo"],"firstnames":["Nicolas"],"suffixes":[]},{"propositions":[],"lastnames":["Lindberg"],"firstnames":["Raija"],"suffixes":[]},{"propositions":[],"lastnames":["Grummel"],"firstnames":["Verena"],"suffixes":[]},{"propositions":[],"lastnames":["Donnellan"],"firstnames":["Naoimh"],"suffixes":[]},{"propositions":[],"lastnames":["Comabella"],"firstnames":["Manuel"],"suffixes":[]},{"propositions":[],"lastnames":["Montalban"],"firstnames":["Xavier"],"suffixes":[]},{"propositions":[],"lastnames":["Kieseier"],"firstnames":["Bernd"],"suffixes":[]},{"propositions":[],"lastnames":["Soelberg","Sørensen"],"firstnames":["Per"],"suffixes":[]},{"propositions":[],"lastnames":["Hartung"],"firstnames":["Hans-Peter"],"suffixes":[]},{"propositions":[],"lastnames":["Derfuss"],"firstnames":["Tobias"],"suffixes":[]},{"propositions":[],"lastnames":["Lawton"],"firstnames":["Andy"],"suffixes":[]},{"propositions":[],"lastnames":["Sikkema"],"firstnames":["Dan"],"suffixes":[]},{"propositions":[],"lastnames":["Pallardy"],"firstnames":["Marc"],"suffixes":[]},{"propositions":[],"lastnames":["Hemmer"],"firstnames":["Bernhard"],"suffixes":[]},{"propositions":[],"lastnames":["Deisenhammer"],"firstnames":["Florian"],"suffixes":[]},{"propositions":[],"lastnames":["Broët"],"firstnames":["Philippe"],"suffixes":[]},{"propositions":[],"lastnames":["Dönnes"],"firstnames":["Pierre"],"suffixes":[]},{"propositions":[],"lastnames":["Davidson"],"firstnames":["Julie"],"suffixes":[]},{"propositions":[],"lastnames":["Fogdell-Hahn"],"firstnames":["Anna"],"suffixes":[]},{"firstnames":[],"propositions":[],"lastnames":["ABIRISK Consortium"],"suffixes":[]}],"year":"2017","pmid":"28170401","pmcid":"PMC5295710","keywords":"Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Antibodies, Child, Child, Preschool, Europe, Female, Humans, Immunologic Factors, Infant, Infant, Newborn, Interferon-beta, Male, Middle Aged, Multiple Sclerosis, Natalizumab, Retrospective Studies, Sex Factors, Time Factors, Young Adult","pages":"e0170395","bibtex":"@article{link_clinical_2017,\n\ttitle = {Clinical practice of analysis of anti-drug antibodies against interferon beta and natalizumab in multiple sclerosis patients in {Europe}: {A} descriptive study of test results},\n\tvolume = {12},\n\tissn = {1932-6203},\n\tshorttitle = {Clinical practice of analysis of anti-drug antibodies against interferon beta and natalizumab in multiple sclerosis patients in {Europe}},\n\tdoi = {10.1371/journal.pone.0170395},\n\tabstract = {Antibodies against biopharmaceuticals (anti-drug antibodies, ADA) have been a well-integrated part of the clinical care of multiple sclerosis (MS) in several European countries. ADA data generated in Europe during the more than 10 years of ADA monitoring in MS patients treated with interferon beta (IFNβ) and natalizumab have been pooled and characterized through collaboration within a European consortium. The aim of this study was to report on the clinical practice of ADA testing in Europe, considering the number of ADA tests performed and type of ADA assays used, and to determine the frequency of ADA testing against the different drug preparations in different countries. A common database platform (tranSMART) for querying, analyzing and storing retrospective data of MS cohorts was set up to harmonize the data and compare results of ADA tests between different countries. Retrospective data from six countries (Sweden, Austria, Spain, Switzerland, Germany and Denmark) on 20,695 patients and on 42,555 samples were loaded into tranSMART including data points of age, gender, treatment, samples, and ADA results. The previously observed immunogenic difference among the four IFNβ preparations was confirmed in this large dataset. Decreased usage of the more immunogenic preparations IFNβ-1a subcutaneous (s.c.) and IFNβ-1b s.c. in favor of the least immunogenic preparation IFNβ-1a intramuscular (i.m.) was observed. The median time from treatment start to first ADA test correlated with time to first positive test. Shorter times were observed for IFNβ-1b-Extavia s.c. (0.99 and 0.94 years) and natalizumab (0.25 and 0.23 years), which were introduced on the market when ADA testing was already available, as compared to IFNβ-1a i.m. (1.41 and 2.27 years), IFNβ-1b-Betaferon s.c. (2.51 and 1.96 years) and IFNβ-1a s.c. (2.11 and 2.09 years) which were available years before routine testing began. A higher rate of anti-IFNβ ADA was observed in test samples taken from older patients. Testing for ADA varies between different European countries and is highly dependent on the policy within each country. For drugs where routine monitoring of ADA is not in place, there is a risk that some patients remain on treatment for several years despite ADA positivity. For drugs where a strategy of ADA testing is introduced with the release of the drug, there is a reduced risk of having ADA positive patients and thus of less efficient treatment. This indicates that potential savings in health cost might be achieved by routine analysis of ADA.},\n\tlanguage = {eng},\n\tnumber = {2},\n\tjournal = {PloS One},\n\tauthor = {Link, Jenny and Ramanujam, Ryan and Auer, Michael and Ryner, Malin and Hässler, Signe and Bachelet, Delphine and Mbogning, Cyprien and Warnke, Clemens and Buck, Dorothea and Hyldgaard Jensen, Poul Erik and Sievers, Claudia and Ingenhoven, Kathleen and Fissolo, Nicolas and Lindberg, Raija and Grummel, Verena and Donnellan, Naoimh and Comabella, Manuel and Montalban, Xavier and Kieseier, Bernd and Soelberg Sørensen, Per and Hartung, Hans-Peter and Derfuss, Tobias and Lawton, Andy and Sikkema, Dan and Pallardy, Marc and Hemmer, Bernhard and Deisenhammer, Florian and Broët, Philippe and Dönnes, Pierre and Davidson, Julie and Fogdell-Hahn, Anna and {ABIRISK Consortium}},\n\tyear = {2017},\n\tpmid = {28170401},\n\tpmcid = {PMC5295710},\n\tkeywords = {Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Antibodies, Child, Child, Preschool, Europe, Female, Humans, Immunologic Factors, Infant, Infant, Newborn, Interferon-beta, Male, Middle Aged, Multiple Sclerosis, Natalizumab, Retrospective Studies, Sex Factors, Time Factors, Young Adult},\n\tpages = {e0170395},\n}\n\n","author_short":["Link, J.","Ramanujam, R.","Auer, M.","Ryner, M.","Hässler, S.","Bachelet, D.","Mbogning, C.","Warnke, C.","Buck, D.","Hyldgaard Jensen, P. 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