TY - JOUR
T1 - Usefulness of tissue inhibitor of metalloproteinase 1 as a predictor of sustained remission in patients with antineutrophil cytoplasmic antibody-associated vasculitis
AU - for the Research Committee of Intractable Vasculitis Syndrome and the Research Committee of Intractable Renal Disease of the Ministry of Health, Labour and Welfare of Japan
AU - Ishizaki, Jun
AU - Takemori, Ayako
AU - Horie, Kenta
AU - Hiraoka, Daisuke
AU - Suemori, Koichiro
AU - Matsumoto, Takuya
AU - Sada, Ken ei
AU - Amano, Koichi
AU - Harigai, Masayoshi
AU - Arimura, Yoshihiro
AU - Makino, Hirofumi
AU - Takenaka, Katsuto
AU - Takemori, Nobuaki
AU - Hasegawa, Hitoshi
AU - Murakawa, Yohko
AU - Muso, Eri
AU - Komatsuda, Atsushi
AU - Ito, Satoshi
AU - Fujii, Takao
AU - Kawakami, Atsushi
AU - Nakaya, Izaya
AU - Saito, Takao
AU - Ito, Takafumi
AU - Hirawa, Nobuhito
AU - Yamamura, Masahiro
AU - Nakano, Masaaki
AU - Nitta, Kosaku
AU - Ogura, Makoto
AU - Naniwa, Taio
AU - Ozaki, Shoichi
AU - Hirahashi, Junichi
AU - Ogawa, Noriyoshi
AU - Hosoya, Tatsuo
AU - Wada, Takashi
AU - Horikoshi, Satoshi
AU - Kawaguchi, Yasushi
AU - Hayashi, Taichi
AU - Yoshida, Masaharu
AU - Watanabe, Tsuyoshi
AU - Inaguma, Daijo
AU - Tsuruya, Kazuhiko
AU - Homma, Noriyuki
AU - Takeuchi, Tsutomu
AU - Nakagawa, Naoki
AU - Takeda, Shinichi
AU - Katabuchi, Ritsuko
AU - Iwano, Masayuki
AU - Atsumi, Tatsuya
AU - Fujimoto, Shoichi
AU - Tsuboi, Naotake
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Background: We previously identified tissue inhibitor of metalloproteinase 1 (TIMP-1) as a biomarker of disease activity that distinguished mildly or highly active antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) from remission 6 months after the initiation of remission-induction therapy. In the present study, we investigated whether TIMP-1 is clinically useful as a predictor of relapse and sustained remission in AAV patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) during maintenance therapy. Methods: The relationship between serum TIMP-1 levels and clinical outcomes in AAV patients receiving maintenance therapy was assessed using the follow-up data of a Japanese large-cohort study (the RemIT-JAV-RPGN study) and data collected from AAV patients on maintenance therapy in our hospital (the MAAV-EU study). Results: In the RemIT-JAV RPGN study, serum levels of TIMP-1 were significantly higher in mildly active AAV patients with MPA and GPA 6 months after the initiation of remission-induction therapy than in patients in remission. Regarding maintenance therapy, elevated levels of TIMP-1 in patients in remission were associated with relapse and/or difficulty reducing the glucocorticoid dosage after 6 to 12 months. In the MAAV-EU study, serum levels of TIMP-1 were elevated in relapsed patients 6 months before relapse, earlier than the increase in serum levels of CRP. Analyses of both studies revealed that approximately 30% of patients in remission with a serum TIMP-1 level ≥ 150 ng/mL relapsed after 6 to 12 months, while the majority of patients with a TIMP-1 level < 150 ng/mL sustained remission for at least 12 months. Conclusion: We herein demonstrated that TIMP-1 is more useful as a predictive biomarker of sustained remission than as a predictor of relapse in maintenance therapy for AAV. TIMP-1 levels < 150 ng/mL are important for the long-term maintenance of remission and may be an indicator for the tapering or cessation of treatment.
AB - Background: We previously identified tissue inhibitor of metalloproteinase 1 (TIMP-1) as a biomarker of disease activity that distinguished mildly or highly active antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) from remission 6 months after the initiation of remission-induction therapy. In the present study, we investigated whether TIMP-1 is clinically useful as a predictor of relapse and sustained remission in AAV patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) during maintenance therapy. Methods: The relationship between serum TIMP-1 levels and clinical outcomes in AAV patients receiving maintenance therapy was assessed using the follow-up data of a Japanese large-cohort study (the RemIT-JAV-RPGN study) and data collected from AAV patients on maintenance therapy in our hospital (the MAAV-EU study). Results: In the RemIT-JAV RPGN study, serum levels of TIMP-1 were significantly higher in mildly active AAV patients with MPA and GPA 6 months after the initiation of remission-induction therapy than in patients in remission. Regarding maintenance therapy, elevated levels of TIMP-1 in patients in remission were associated with relapse and/or difficulty reducing the glucocorticoid dosage after 6 to 12 months. In the MAAV-EU study, serum levels of TIMP-1 were elevated in relapsed patients 6 months before relapse, earlier than the increase in serum levels of CRP. Analyses of both studies revealed that approximately 30% of patients in remission with a serum TIMP-1 level ≥ 150 ng/mL relapsed after 6 to 12 months, while the majority of patients with a TIMP-1 level < 150 ng/mL sustained remission for at least 12 months. Conclusion: We herein demonstrated that TIMP-1 is more useful as a predictive biomarker of sustained remission than as a predictor of relapse in maintenance therapy for AAV. TIMP-1 levels < 150 ng/mL are important for the long-term maintenance of remission and may be an indicator for the tapering or cessation of treatment.
KW - Antineutrophil cytoplasmic antibody-associated vasculitis
KW - Biomarker
KW - Maintenance therapy
KW - Remission
KW - Tissue inhibitor of metalloproteinase 1
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U2 - 10.1186/s13075-021-02471-5
DO - 10.1186/s13075-021-02471-5
M3 - Article
C2 - 33743769
AN - SCOPUS:85102726074
SN - 1478-6354
VL - 23
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
IS - 1
M1 - 91
ER -