title: Concomitant methotrexate and tacrolimus augment the clinical response to abatacept in patients with rheumatoid arthritis with a prior history of biological DMARD use.
abstract: This observational retrospective study examined whether abatacept efficacy could be augmented with concomitant methotrexate (MTX) or tacrolimus (TAC) in patients with rheumatoid arthritis (RA) who experienced failure with prior biological disease-modifying antirheumatic drugs (DMARDs) and in whom favorable therapeutic efficacy is difficult to achieve. All patients with a prior biological DMARD history who were treated with abatacept for 52 weeks and registered in a Japanese multicentre registry were included. Clinical efficacy and safety of abatacept according to the concomitant drug used, i.e., none (ABT-mono), MTX (ABT-MTX), and TAC (ABT-TAC), were compared. A greater mean percent change of DAS28-ESR was observed in the ABT-TAC group compared with the ABT-mono group at weeks 12 (-20.5 vs. -5.4 %, p = 0.035) and 24 (-25.0 vs. -11.0 %, p = 0.036). ABT-MTX and ABT-TAC groups had a significantly higher proportion of patients who achieved low disease activity (LDA) within 52 weeks compared with the respective baselines, while no significant change was observed in the ABT-mono group. A higher proportion of patients in the ABT-TAC group achieved EULAR moderate response compared with the ABT-mono group at week 52 (66.7 vs. 35.0 %, p = 0.025). Multivariate logistic regression analysis revealed that concomitant TAC use was independently associated with the achievement of LDA and EULAR response at 52 weeks, while concomitant MTX use was not. Concomitant TAC use may offer a suitable option for RA patients treated with abatacept after prior biological DMARD failure, likely because both abatacept and TAC affect T cell activation.
authors.affiliation: Department of Orthopedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan. nobunori@med.nagoya-u.ac.jp.
authors.forename: Nobunori
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Department of Orthopedic Surgery, Konan Kosei Hospital, 137 Oomatsubara, Takaya-cho, Konan, Aichi, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Fujibayashi
authors.affiliation: Department of Orthopedic Surgery and Rheumatology, Nagoya Medical Center, 4-1-1 Sanno-maru, Naka-ku, Nagoya, Aichi, Japan.
authors.forename: Daihei
authors.initials: D
authors.lastname: Kida
authors.affiliation: Department of Rheumatology, Toyohashi Municipal Hospital, 50 Hakken-nishi, Aotake-cho, Toyohashi, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hirano
authors.affiliation: Kato Orthopedic Clinic, 8-4 Minami-myoudaiji-cho, Okazaki, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Orthopedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Daizo
authors.initials: D
authors.lastname: Kato
authors.affiliation: Saito Clinic, 1-10 Heiwagaoka, Meito-ku, Nagoya, Aichi, Japan.
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Saito
authors.affiliation: Department of Orthopedic Surgery and Rheumatology, Nagoya Medical Center, 4-1-1 Sanno-maru, Naka-ku, Nagoya, Aichi, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kaneko
authors.affiliation: Department of Rheumatology, Tokyo Kosei Nenkin Hospital, 5-1 Tsukudo-cho, Shinjuku-ku, Tokyo, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yabe
authors.affiliation: Department of Orthopedic Surgery, Nagoya Central Hospital, 3-7-7 Taiko, Nakamura-ku, Nagoya, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Takagi
authors.affiliation: Department of Orthopedic Surgery, Anjo Kosei Hospital, 28 Higashihirokute, Anjo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Oguchi
authors.affiliation: Department of Orthopedic Surgery, Ichinomiya Municipal Hospital, 2-2-22 Bunkyo, Ichinomiya, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyake
authors.affiliation: Department of Orthopedic Surgery, Kariya-Toyota General Hospital, 5-15 Sumiyoshi-cho, Kariya, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Rheumatology, Nagano Red Cross Hospital, 5-22-1 Wakazato, Nagano, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Department of Orthopedic Surgery, Toyota Kosei Hospital, 500-1 Ibohara, Josui-cho, Toyota, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Kanayama
authors.affiliation: Department of Orthopedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Funahashi
authors.affiliation: Department of Orthopedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hanabayashi
authors.affiliation: Department of Orthopedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Hirabara
authors.affiliation: Department of Orthopedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Asai
authors.affiliation: Department of Orthopedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Toki
authors.initials: T
authors.lastname: Takemoto
authors.affiliation: Department of Orthopedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Kenya
authors.initials: K
authors.lastname: Terabe
authors.affiliation: Department of Orthopedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Asai
authors.affiliation: Department of Orthopedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshioka
authors.affiliation: Department of Orthopedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishiguro
authors.affiliation: Department of Orthopedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Kojima
mesh_terms: D000069594:Abatacept / Q000627:therapeutic use*; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D012074:Remission Induction; D012189:Retrospective Studies; D016559:Tacrolimus / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D000069594:Abatacept; D016559:Tacrolimus; D008727:Methotrexate
keywords: Abatacept; Biological DMARDs; Methotrexate; Rheumatoid arthritis; Tacrolimus