Natalizumab-related anaphylactoid reactions in MS patients are associated with HLA class II alleles.

OBJECTIVES We aimed to investigate potential associations between human leukocyte antigen (HLA) class I and class II alleles and the development of anaphylactic/anaphylactoid reactions in patients with multiple sclerosis (MS) treated with natalizumab. METHODS HLA class I and II genotyping was performed in patients with MS who experienced anaphylactic/anaphylactoid reactions and in patients who did not develop infusion-related allergic reactions following natalizumab administration. RESULTS A total of 119 patients with MS from 3 different cohorts were included in the study: 54 with natalizumab-related anaphylactic/anaphylactoid reactions and 65 without allergic reactions. HLA-DRB1*13 and HLA-DRB1*14 alleles were significantly increased in patients who developed anaphylactic/anaphylactoid reactions (p M-H = 3 × 10(-7); odds ratio [OR]M-H = 8.96, 95% confidence interval [CI] = 3.40-23.64), with a positive predictive value (PPV) of 82%. In contrast, the HLA-DRB1*15 allele was significantly more represented in patients who did not develop anaphylactic/anaphylactoid reactions to natalizumab (p M-H = 6 × 10(-4); ORM-H = 0.2, 95% CI = 0.08-0.50), with a PPV of 81%. CONCLUSIONS HLA-DRB1 genotyping before natalizumab treatment may help neurologists to identify patients with MS at risk for developing serious systemic hypersensitivity reactions associated with natalizumab administration.

Journal Article;

The “Red Española de Esclerosis Múltiple (REEM)” sponsored by the FEDER-FIS, FEDER-FIS PI13/0879 and the “Ajuts per donar Suport als Grups de Recerca de Catalunya,” sponsored by the “Agència de Gestió d’Ajuts Universitaris i de Recerca” (AGAUR), Generalitat de Catalunya, Spain. The study was also funded with a FP7 grant “Best MS”: Best Escalation Treatment in Multiple Sclerosis (MS), Grant agreement no: 305477. French patients were included in the BIONAT cohort funded by the French Ministry of Health (Projet Hospitalier de Recherche Clinique, PHRC 2008 (grant agreement no: 2008-005906-38 and clinicaltrials.org identifier NCT00942214) and the French MS Society (ARSEP 2007, 2008, 2010)