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ACR 2017 | Daily Highlights
Relation of HLA-DRB1 Genotype to the Efficacies of Abatacept and Tocilizumab in Patients with Rheumatoid Arthritis
Authors: Kensuke Oryoji, The Center for Rheumatology, Matsuyama Red Cross Hospital, Ehime, Japan
To investigate whether clinical efficacy of abatacept (ABT) and tocilizumab (TCZ) differs depending on whether or not HLA-DRB1 Shared Epitope (SE) is present in patients with rheumatoid arthritis.
HLA-DRB1 genotype of patients treated with ABT(n=78) and TCZ (n=78) was identified. HLA-DRB1 0101,0102,0401,0404,0405,0408,1001 was defined as SE. Retention rate and clinical efficacy were assessed by Cox proportional hazard model and multiple regression analysis.
The patients with SE positive were 51 in ABT (65%) and 53 in TCZ (68%). The retention rate of ABT was significantly higher in SE positive patients than in SE negatives. (p <0.0001,log rank),and the retention rate of TCZ was not significantly different in both group.
Average CDAI at 24 week was 3.5/10.7 in SE positive/negative group with ABT (p <0.0001, ANOVA), and 6.3/5.8 with TCZ (p = 0.87). Multivariable Cox hazard regression model, in which age, sex, disease duration, ACPA titer, RF titer , MHAQ, prior use of biological agents, MTX dose, oral steroid dose, and SDAI and CRP at baseline were adjusted, revealed that, compared with SE-positive, SE-negative had a higher abatacept discontinuation due to lack of efficacy (adjusted HR=9.2, 95% CI: 2.8-30.4), but was not significant in TCZ (p = 0.41). In addition, the predictor of CDAI at 24 week by multiple regression analysis was SE (p<0.0001) in ABT but SE was not predictive in TCZ.
ABT is effective in SE positive group, but TCZ is not relevant for SE.
K. Oryoji, Abbvie, Chugai, Tanabe-Mitsubishi, Astellas, Eisai, Janssen, Pfizer, UCB, Ono., 8;
Finally, it appears that efforts to categorize patients for responses to given therapeutic approaches are giving meaningful results. HLA-DRB1 alleles often referred to as the “shared epitope” (SE), have been associated with the occurrence and severity of rheumatoid arthritis. The retention rate of abatacept in SE positive cases was significantly higher than in negative cases (p < 0001), whereas in the tocilizumab group it was not significantly different.
If confirmed, the results indicate that tocilizumab efficacy does not depend on the presence of SE. In contrast, negative SE could imply failure to remain on abatacept.
Prof. Dr. Paul Hasler