The cross-reactivity of binding antibodies with different interferon beta formulations used as disease-modifying drugs in multiple sclerosis patients.
Interferon beta (IFNb) preparations are commonly used as first-line therapy in relapsing-remitting multiple sclerosis (RRMS). They are, however, characterized by limited efficacy, partly due to the formation of anti-IFNb antibodies in patients.In this pilot study, we assessed with the ELISA method the presence of the binding antibodies (BAbs) against interferon beta after 2 years of therapy with subcutaneous interferon beta 1a (Rebif) in 49 RRMS patients. Antibody levels were established again within 1 year after treatment withdrawal. We used 3 interferons that are commercially available for MS therapy, namely Avonex (Biogen Idec Limited), Rebif (Merck Serono), and Betaferon (Bayer Pharma AG), as antigens.BAbs reacting with Rebif were found in 24.4% to 55% of patients, depending on the units of their expression. The levels of anti-Rebif antibodies remained high in 8 patients and in 4 patients they dropped significantly. Strong correlations were obtained in all assays (anti-Rebif-anti-Avonex, anti-Rebif-anti-Betaferon, and anti-Betaferon-anti-Avonex) and the existence of cross-reactivity in the formation of antibodies against all the tested formulations of interferon beta was confirmed. The levels of BAbs remain significant in the clinical context, and their assessment is the first choice screening; however, methods of BAbs evaluation can be crucial for further decisions. More studies are needed to confirm our results; specifically it would be of interest to evaluate methods of neutralizing antibodies identification, as we only assessed the binding antibodies. Nevertheless, our results support the concept that in interferon nonresponders, that are positive for binding antibodies, switching the therapy to alternative disease-modifying agent (for example glatiramer acetate, fingolimod, or natalizumab) is justified, whereas the switch to another interferon formulation will probably be of no benefit.
Department of Developmental Neurology, Poznan University of Medical Sciences, Przybyszewskiego Department of Neurochemistry and Neuropathology, Poznan University of Medical Sciences, Przybyszewskiego Department of General and Vascular Surgery and Angiology, Poznan University of Medical Sciences, prof. L. Bierkowski Hospital Department of Neurology and Cerebrovascular Disorders, Poznan University of Medical Sciences, prof. L. Bierkowski Hospital, Poznan, Poland.
Agnieszka
A
Wencel-Warot
Slawomir
S
Michalak
Marcin
M
Warot
Alicja
A
Kalinowska-Lyszczarz
Radoslaw
R
Kazmierski
D000328:Adult; D000906:Antibodies / Q000276:immunology*; D003429:Cross Reactions; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a / Q000276:immunology* / Q000627:therapeutic use*; D000068576:Interferon beta-1b / Q000276:immunology* / Q000627:therapeutic use*; D016899:Interferon-beta / Q000276:immunology* / Q000627:therapeutic use*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology*; D010865:Pilot Projects; D011446:Prospective Studies
D000906:Antibodies; D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a