HLA Genes and Interferon-beta Preparations Influence Risk of Developing Neutralizing Anti-Drug Antibodies in Multiple Sclerosis (P1.213)

OBJECTIVE: To investigate if HLA allele group carriage influences the risk of developing neutralizing anti-drug antibodies (NAb) in multiple sclerosis (MS) patients treated with interferon-beta. BACKGROUND: HLA alleles are known risk factors for susceptibility for MS. Only a proportion of all patients receiving interferon-beta develops NAbs. When present at high-titer levels they are associated with a loss of biological efficacy and have the capacity to block endogenous interferon-beta. For different interferon-beta preparations the proportion of NAb positive patients is different, being the highest for interferon-beta-1b given subcutaneously. DESIGN/METHODS: Cross-referencing HLA and NAb-registries resulted in 364 NAb positive patients and 539 NAb negative patients. HLA genotypes were obtained from either Olerup SSP HLA low resolution Kits, Luminex based reverse SSO or imputation from SNP data (GWAS or Immunochip). Biologically relevant titers were defined as a NAb titer >150 TRU/ml. RESULTS: HLA-DRB1*15 carriage was shown to increase the risk of developing NAbs for interferon-beta-1a and decrease the risk for interferon-beta-1b. The opposite effect is observed for DRB1*04. The absolute risk is lowest for IFNB-1a injected intramuscularly regardless of HLA carriage. CONCLUSIONS: The interferon-beta preparation still remains the single most significant determinant for the risk of developing NAbs in MS. HLA allele group carriage influences the risk of NAbs differently within interferon-beta-1a and interferon-beta-1b treated MS patients. Disclosure: Dr. Fink has received personal compensation for activities with Novartis. Ms. Link has received research support from Karolinska Institute. Ms. Lundkvist has received research support from Biogen Idec. Dr. Hermanrud has nothing to disclose. Dr. Lima has nothing to disclose. Dr. Brynedal has received research support from the Swedish Research Council. Dr. Kockum has nothing to disclose. Dr. Hillert has received personal compensation for activities with Biogen Idec as an advisory board member, with Merck Serono as a consultant, and with Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience as a speaker. Dr. Hillert has received research support from Sanofi-Aventis Pharmaceuticals Inc., Bayer Schering, Biogen Idec, and Merck Serono. Dr. Fogdell-Hahn has received research support from Biogen Idec, Merck Serono and Sanofi-Aventis Pharmaceuticals, Inc.