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

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 (IFN beta) 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 IFN beta preparations was confirmed in this large dataset. Decreased usage of the more immunogenic preparations IFN beta-1a subcutaneous (s.c.) and IFN beta-1b s.c. in favor of the least immunogenic preparation IFN beta-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 IFN beta-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 IFN beta-1a i. m. (1.41 and 2.27 years), IFN beta-1b-Betaferon s. c. (2.51 and 1.96 years) and IFN beta-1a s. c. (2.11 and 2.09 years) which were available years before routine testing began. A higher rate of anti-IFN beta ADA was observed in
QC 20170321