title: Interleukin-6-receptor polymorphisms rs12083537, rs2228145, and rs4329505 as predictors of response to tocilizumab in rheumatoid arthritis.
abstract: 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.
authors: aDepartment of Infectious Diseases and Rheumatology, Institute for Inflammation Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen bDepartment of Rheumatology, Copenhagen University Hospital, Gentofte cDepartment of Rheumatology, Aarhus University Hospital, Aarhus dDepartment of Rheumatology, Odense University Hospital, Odense, Denmark.
authors: Christian
authors: C
authors: Enevold
authors: Bo
authors: B
authors: Baslund
authors: Louise
authors: L
authors: Linde
authors: Norah L
authors: NL
authors: Josephsen
authors: Ulrik
authors: U
authors: Tarp
authors: Hanne
authors: H
authors: Lindegaard
authors: Søren
authors: S
authors: Jacobsen
authors: Claus H
authors: CH
authors: Nielsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D018501:Antirheumatic Agents / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019947:Receptors, Interleukin-6 / Q000235:genetics*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D019947:Receptors, Interleukin-6; C502936:tocilizumab