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Abstract
Background Abatacept, a soluble fusion protein composed of the extracellular domain of CTLA-4 molecule and the Fc portion of human IgG1, is approved therapy for RA by the mechanism of binding to CD80/86 (B7–1/B7–2) on antigen presenting cell (APC), and blocking the B7:CD28 interaction. Meanwhile, it is suggested that HLA-DRB1 shared epitope (SE) associates with the production of ACPA through MHC molecule-based antigen presentation. Moreover, the association between the efficacy of abatacept and the positivity for anti-cyclic citrullinated peptide antibody (ACPA) was reported. Thus, we speculated that there may be correlation between the efficacy of abatacept and patients' HLA-DRB1 SE positivity, so we investigated correlation between the clinical efficacy of abatacept in RA patients and their HLA-DRB1 genotype.
Objectives To identify the relation between the efficacy of abatacept on patients with rheumatoid arthritis (RA) and their HLA-DRB1 phenotype including whether having shared epitope (SE).
Methods HLA-DRB1 phenotype of 72 patients treated with abatacept was identified, and divided into 2 group, SE (HLA-DRB1 0101, 0401, 0404, 0405, 0408, 1001) positive and SE negative. To overcome potential bias, multivariate logistic regression analysis was done in this retrospective cohort.
Results They were divided into 47 SE positive patients (65.3%) and 25 SE negative patients (34.7%). The retention rate of abatacept treatment at week 52 were 95.3%/47.1% (SE positive/SE negative, p<0.0001, log-rank test), respectively. Adjusted hazard ratio for abatacept discontinuation due to lack of efficacy was 8.94 (95% CI: 2.95–34.1, p<0.0001, Multivariable Cox proportional hazards regression model) in SE negative group compared to SE positive group. The EULAR good response rate at week 24 were 74.5%/20.0% (SE positive/SE negative, p<0.0001, Fisher's exact test), respectively. Simplified Disease Activity Index (SDAI) remission rate at week 24 were 55.3%/20.0% (SE positive/SE negative, p=0.004, Fisher's exact test), respectively. Multivariate logistic regression revealed the odds ratio of EULAR good response and SDAI remission achievement in SE positive patients was 23.2 and 6.73 (95% CI: 5.10–152.0, p<0.0001 and 1.70–32.3, p=0.006), respectively.
Conclusions Abatacept is strictly effective to SE positive RA patients.
Disclosure of Interest K. Oryoji Grant/research support from: Ono, Speakers bureau: Abbvie, Chugai, Astellas, Mitsubishi-Tanabe, Pfizer, Janssen, Eisai, UCB and Ono, K. Yoshida: None declared, S.-I. Mizuki Speakers bureau: Abbvie, Astellas, Mitsubishi-Tanabe, Pfizer, Janssen, Eisai, UCB and Ono