Impact of the HLA-DRB1 shared epitope on responses to treatment with tofacitinib or abatacept in patients with rheumatoid arthritis

• Published in: Arthritis research & therapy Vol. 23; no. 1; pp. 1 - 228
• Main Authors: Hirose, Wataru, Harigai, Masayoshi, Amano, Koichi, Hidaka, Toshihiko, Itoh, Kenji, Aoki, Kazutoshi, Nakashima, Masahiro, Nagasawa, Hayato, Komano, Yukiko, Nanki, Toshihiro, Akiyama, Yuji, Ando, Souichirou, Hashiba, Yayoi, Kaneko, Motohide, Kawagoe, Mitsuhiro, Kondo, Tsuneo, Kubo, Kazuyoshi, Masuda, Ikuko, Matsumoto, Mitsuyo, Okada, Yusuke, Shibata, Akiko, Suzuki, Kimihiro, Takamatsu, Ko, Takei, Hirofumi
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 31.08.2021; BioMed Central; BMC
• Subjects: Abatacept; Antigenic determinants; Arthritis; Bias; Clinical outcomes; Dosage and administration; Drug therapy; Drugs; Enrollments; Genetic aspects; Health aspects; Histocompatibility antigens; HLA histocompatibility antigens; Patient outcomes; Patients; Physiological aspects; Propensity score matching; Remission (Medicine); Retention; Rheumatoid arthritis; Rheumatology; Shared epitope; Tofacitinib; Japan
• DOI: 10.1186/s13075-021-02612-w
• ISSN: 1478-6362; 1478-6354

Abstract Objectives The aim of this study was to compare the clinical effectiveness of tofacitinib and abatacept and clarify the impact of the HLA-DRB1 shared epitope (SE) on responses to these treatments in patients with rheumatoid arthritis (RA). Methods After adjustments by propensity score matching, 70 out of 161 patients receiving tofacitinib and 70 out of 131 receiving abatacept were extracted. The clinical effectiveness of both drugs over 24 weeks and the impact of the copy numbers of SE on effectiveness outcomes were investigated. Results The percentage of patients in remission in the 28-joint count disease activity score using the erythrocyte sedimentation rate (DAS28-ESR) did not significantly differ between patients receiving tofacitinib and abatacept at week 24 (32% vs 37%, p = 0.359). The mean change at week 4 in DAS28-ESR from baseline was significantly greater in patients receiving tofacitinib than in those receiving abatacept (− 1.516 vs − 0.827, p = 0.0003). The percentage of patients in remission at week 4 was 30% with tofacitinib and 15% with abatacept ( p = 0.016). When patients were stratified by the copy numbers of SE alleles, differences in these numbers did not affect DAS28-ESR scores of patients receiving tofacitinib. However, among patients receiving abatacept, DAS28-ESR scores were significantly lower in patients carrying 2 copies of SE alleles than in those carrying 0 copies at each time point throughout the 24-week period. Furthermore, the percentage of patients in remission with DAS28-ESR at week 24 was not affected by the copy numbers of SE alleles in patients receiving tofacitinib ( p = 0.947), whereas it significantly increased as the copy numbers became higher in patients receiving abatacept ( p = 0.00309). Multivariable logistic regression analyses showed a correlation between the presence of SE and DAS28-ESR remission in patients receiving abatacept (OR = 25.881, 95% CI = 3.140–213.351, p = 0.0025), but not in those receiving tofacitinib (OR = 1.473, 95% CI = 0.291–7.446, p = 0.639). Conclusions Although the clinical effectiveness of tofacitinib and abatacept was similar at week 24, tofacitinib was superior to abatacept for changes from baseline in DAS28-ESR and the achievement of remission at week 4. SE positivity was associated with the achievement of DAS28-ESR remission by week 24 in patients receiving abatacept, but not in those receiving tofacitinib.