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Tocilizumab (TCZ), a monoclonal antibody targeting the human interleukin-6-receptor (IL-6R), is indicated for the treatment of rheumatoid arthritis (RA). We examined whether three IL6R single-nucleotide polymorphisms rs12083537, rs2228145 (formerly rs8192284), and rs4329505 with previously reported functional effects were associated with clinical response to TCZ in a retrospective study cohort consisting of 79 RA patients. Three months after initiation of TCZ therapy, changes in swollen joint count (SJC) and, subordinately, tender joint count (TJC), serum-CRP, DAS28-CRP, and EULAR-response were tested for association with the IL6R-haplotype or genotype. The major allele (A) of rs12083537 and the minor allele (C) of rs4329505 were associated with a poor SJC response (P=0.02 and 0.02, respectively). Moreover, the AAC-haplotype (for rs12083537, rs2228145, and rs4329505, respectively) was associated with a poor SJC response (P=0.00004) and, with borderline significance, EULAR-response (P=0.05). These data suggest that genetic variation in IL6R may aid in predicting TCZ therapy outcome in RA patients.

Original publication

DOI

10.1097/FPC.0000000000000071

Type

Journal article

Journal

Pharmacogenet Genomics

Publication Date

08/2014

Volume

24

Pages

401 - 405

Keywords

Adult, Aged, Aged, 80 and over, Alleles, Antibodies, Monoclonal, Humanized, Antirheumatic Agents, Arthritis, Rheumatoid, Female, Haplotypes, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Receptors, Interleukin-6, Retrospective Studies, Young Adult