Association of HLA-DRB1 alleles with clinical responses to the anti-interleukin-17A monoclonal antibody secukinumab in active rheumatoid arthritis

Burmester, Gerd R.; Durez, Patrick; Shestakova, Galina; Genovese, Mark C.; Schulze-Koops, Hendrik; Li, Yue; Wang, Ying A.; Lewitzky, Steve; Koroleva, Irina; Berneis, Anni Agarwal; Lee, David M. und Hueber, Wolfgang (2016): Association of HLA-DRB1 alleles with clinical responses to the anti-interleukin-17A monoclonal antibody secukinumab in active rheumatoid arthritis. In: Rheumatology, Bd. 55, Nr. 1: S. 49-55

Abstract

Objective. To assess whether preliminary findings of associations between the HLA-DRB1* 04 and HLADRB1*shared epitope (SE) allelic groups and response to the anti-IL-17A mAb secukinumab in RA were reproducible in an independent RA cohort. Methods. Biologic-naive subjects (n = 100) with RA by 2010 criteria with tender/swollen joint counts (each 56) and high-sensitivity CRP (hsCRP) > 10 mg/l were randomized 2: 1 to secukinumab 10 mg/kg i.v. or placebo every 2 weeks until week 10. Potential associations with treatment response to secukinumab at week 12 (DAS28-CRP change from baseline by analysis of covariance, ACR20 response rate by logistic regression) were assessed for HLA-DRB1* 04 (primary end point), HLA-DRB1* SE and HLA-DRB1 position 11 V/L (HLA-DRB1* pos11 V/L) allelic groups, and baseline levels of hsCRP, RF and anti-CCP. Results. Secukinumab was significantly more effective than placebo in reducing DAS28-CRP (-2.41 vs -0.71;P<0.0001) and producing ACR20 responses (87.1% vs 25.0%;P<0.0001) at week 12. The HLA-DRB1* 04 allelic group was not significantly related to secukinumab response vs placebo. For change from baseline in DAS28-CRP, HLA-DRB1* SE (P = 0.003) and HLA-DRB1* pos11 V/L (P = 0.002) allelic groups were associated with positive treatment response. Higher RF levels, but not anti-CCP positivity, were significantly associated with DAS28-CRP reductions (P = 0.015) and ACR20 (P = 0.008) responses. Secukinumab was well tolerated. Conclusion. Secukinumab significantly reduced signs and symptoms of RA vs placebo. As the HLA-DRB1* SE and HLA-DRB1* pos11 V/L results were driven by lack of placebo response in carriers, the hypothesis of clinical utility for HLA-DRB1* allelic groups in RA anti-IL-17A short-term response prediction could not be corroborated.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1462-0324
• Sprache: Englisch