Contributions
Abstract: P712
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background and aims: Rituximab is a chimeric monoclonal anti-CD20 B-lymphocyte depleting antibody used off-label in multiple sclerosis (MS). The clinical relevance of anti-drug antibodies (ADA) against rituximab in MS is currently unknown. We here sought to determine the frequency of ADA using an in-house validated electrochemiluminescent (ECL) immunoassay and a commercial enzyme-linked immunosorbent assay (ELISA) to compare methods.
Method: Cross-sectional study in 339 MS patients with variable treatment duration (mean treatment duration 1.54 ± 0.84 (0.4 - 5.3) years) immediately before a scheduled rituximab infusion. Occurrence of rituximab ADA was related to B-lymphocyte counts, allergic reactions and clinical efficacy (relapses and contrast-enhancing lesions on magnetic resonance imaging) derived from review of clinical charts.
Results: The ECL method was significantly more sensitive than the ELISA method, with 5.6% of the cohort detected as positive with ELISA compared to 32.7% with ECL. Using data from the latter platform rituximab ADA were detected in 37% of relapsing-remitting MS and 26.5% in progressive MS. The presence of ADA decreased with increasing number of rituximab infusions. There was a significant association between both presence and titres of ADA, and incomplete B-lymphocyte depletion, but not with infusion/adverse reactions at the group level. There was no significant difference in clinical outcomes between ADA positive and negative patients, but the power to detect a difference was low due to few events of insufficient treatment effect (ten events in nine patients). Only five patients terminated rituximab during follow up, four of which were ADA positive.
Conclusions: Collectively, these findings suggest that rituximab ADA is common in treated MS patients, but that the frequency decreases with increasing number of rituximab infusions. Furthermore, while ADA correlates with duration of B-lymphocyte depletion, there was no significant difference between ADA positive and negative patients regarding clinical outcomes. Further studies are needed to adress long term implications of rituximab ADA.
Disclosure: The research leading to these results were conducted as part of the ABIRISK consortium (Anti-Biopharmaceutical Immunization: Prediction and analysis of clinical relevance to minimize the risk). For further information, please refer to www.abirisk.eu.
Research reported in this article was partially funded through a Patient-Centered Outcomes Research Institute (PCORI) Award (MS-1511-33196). The statements in this article are solely the responsibility of the authors and do not necessarily represent the views of the Patient-Centered Outcomes Research Institute (PCORI), its Board of Governors or Methodology Committee.
Nicky Dunn, Alexander Juto, Malin Ryner, Ali Manouchehrinia and Luca Piccoli report no conflicts of interest.
Katharina Fink has received unrestricted research grant from Biogen.
Anna Fogdell-Hahn has received unrestricted grants from Biogen and Pfizer and compensation from lectures and invited speaker from Sanofi, Biogen and Pfizer.
Fredrik Piehl has received unrestricted academic research grants from Biogen, Genzyme and Novartis, and travel support and/or compensation for lectures and/or participation in advisory boards from Biogen, Merckserono, Novartis, Genzyme and Teva, which have been exclusively used for the support of research activities.
Abstract: P712
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background and aims: Rituximab is a chimeric monoclonal anti-CD20 B-lymphocyte depleting antibody used off-label in multiple sclerosis (MS). The clinical relevance of anti-drug antibodies (ADA) against rituximab in MS is currently unknown. We here sought to determine the frequency of ADA using an in-house validated electrochemiluminescent (ECL) immunoassay and a commercial enzyme-linked immunosorbent assay (ELISA) to compare methods.
Method: Cross-sectional study in 339 MS patients with variable treatment duration (mean treatment duration 1.54 ± 0.84 (0.4 - 5.3) years) immediately before a scheduled rituximab infusion. Occurrence of rituximab ADA was related to B-lymphocyte counts, allergic reactions and clinical efficacy (relapses and contrast-enhancing lesions on magnetic resonance imaging) derived from review of clinical charts.
Results: The ECL method was significantly more sensitive than the ELISA method, with 5.6% of the cohort detected as positive with ELISA compared to 32.7% with ECL. Using data from the latter platform rituximab ADA were detected in 37% of relapsing-remitting MS and 26.5% in progressive MS. The presence of ADA decreased with increasing number of rituximab infusions. There was a significant association between both presence and titres of ADA, and incomplete B-lymphocyte depletion, but not with infusion/adverse reactions at the group level. There was no significant difference in clinical outcomes between ADA positive and negative patients, but the power to detect a difference was low due to few events of insufficient treatment effect (ten events in nine patients). Only five patients terminated rituximab during follow up, four of which were ADA positive.
Conclusions: Collectively, these findings suggest that rituximab ADA is common in treated MS patients, but that the frequency decreases with increasing number of rituximab infusions. Furthermore, while ADA correlates with duration of B-lymphocyte depletion, there was no significant difference between ADA positive and negative patients regarding clinical outcomes. Further studies are needed to adress long term implications of rituximab ADA.
Disclosure: The research leading to these results were conducted as part of the ABIRISK consortium (Anti-Biopharmaceutical Immunization: Prediction and analysis of clinical relevance to minimize the risk). For further information, please refer to www.abirisk.eu.
Research reported in this article was partially funded through a Patient-Centered Outcomes Research Institute (PCORI) Award (MS-1511-33196). The statements in this article are solely the responsibility of the authors and do not necessarily represent the views of the Patient-Centered Outcomes Research Institute (PCORI), its Board of Governors or Methodology Committee.
Nicky Dunn, Alexander Juto, Malin Ryner, Ali Manouchehrinia and Luca Piccoli report no conflicts of interest.
Katharina Fink has received unrestricted research grant from Biogen.
Anna Fogdell-Hahn has received unrestricted grants from Biogen and Pfizer and compensation from lectures and invited speaker from Sanofi, Biogen and Pfizer.
Fredrik Piehl has received unrestricted academic research grants from Biogen, Genzyme and Novartis, and travel support and/or compensation for lectures and/or participation in advisory boards from Biogen, Merckserono, Novartis, Genzyme and Teva, which have been exclusively used for the support of research activities.