Interleukin-6-receptor polymorphisms rs12083537, rs2228145, and rs4329505 as predictors of response to tocilizumab in rheumatoid arthritis

TY - JOUR

T1 - Interleukin-6-receptor polymorphisms rs12083537, rs2228145, and rs4329505 as predictors of response to tocilizumab in rheumatoid arthritis

AU - Enevold, Christian

AU - Baslund, Bo

AU - Linde, Louise

AU - Josephsen, Norah L

AU - Tarp, Ulrik

AU - Lindegaard, Hanne

AU - Jacobsen, Søren

AU - Nielsen, Claus H

PY - 2014/8

Y1 - 2014/8

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Alleles

KW - Antibodies, Monoclonal, Humanized

KW - Antirheumatic Agents

KW - Arthritis, Rheumatoid

KW - Female

KW - Haplotypes

KW - Humans

KW - Male

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Receptors, Interleukin-6

KW - Retrospective Studies

KW - Young Adult

U2 - 10.1097/fpc.0000000000000071

DO - 10.1097/fpc.0000000000000071

M3 - Letter

C2 - 24978393

SN - 1744-6872

VL - 24

SP - 401

EP - 405

JO - Pharmacogenetics

JF - Pharmacogenetics

IS - 8

ER -