TY - JOUR
T1 - Clinical practice of analysis of anti-drug antibodies against interferon beta and natalizumab in multiple sclerosis patients in Europe
T2 - A descriptive study of test results
AU - Link, Jenny
AU - Ramanujam, Ryan
AU - Auer, Michael
AU - Ryner, Malin
AU - Hässler, Signe
AU - Bachelet, Delphine
AU - Mbogning, Cyprien
AU - Warnke, Clemens
AU - Buck, Dorothea
AU - Hyldgaard Jensen, Poul Erik
AU - Sievers, Claudia
AU - Ingenhoven, Kathleen
AU - Fissolo, Nicolas
AU - Lindberg, Raija
AU - Grummel, Verena
AU - Donnellan, Naoimh
AU - Comabella, Manuel
AU - Montalban, Xavier
AU - Kieseier, Bernd
AU - Soelberg Sørensen, Per
AU - Hartung, Hans-Peter
AU - Derfuss, Tobias
AU - Lawton, Andy
AU - Sikkema, Dan
AU - Pallardy, Marc
AU - Hemmer, Bernhard
AU - Deisenhammer, Florian
AU - Broët, Philippe
AU - Dönnes, Pierre
AU - Davidson, Julie
AU - Fogdell-Hahn, Anna
AU - ABIRISK Consortium
PY - 2017/2
Y1 - 2017/2
N2 - 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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Age Factors
KW - Aged
KW - Aged, 80 and over
KW - Antibodies/immunology
KW - Child
KW - Child, Preschool
KW - Europe
KW - Female
KW - Humans
KW - Immunologic Factors/adverse effects
KW - Infant
KW - Infant, Newborn
KW - Interferon-beta/adverse effects
KW - Male
KW - Middle Aged
KW - Multiple Sclerosis/drug therapy
KW - Natalizumab/adverse effects
KW - Retrospective Studies
KW - Sex Factors
KW - Time Factors
KW - Young Adult
U2 - 10.1371/journal.pone.0170395
DO - 10.1371/journal.pone.0170395
M3 - Journal article
C2 - 28170401
SN - 1932-6203
VL - 12
JO - PLOS ONE
JF - PLOS ONE
IS - 2
M1 - e0170395
ER -