학술논문
Increased Risk of Thyroid Dysfunction by PD-1 and CTLA-4 Blockade in Patients Without Thyroid Autoantibodies at Baseline
Clinical Research Article
Clinical Research Article
Document Type
Academic Journal
Author
Iwama, Shintaro; Kobayashi, Tomoko; Yasuda, Yoshinori; Okuji, Takayuki; Ito, Masaaki; Ando, Masahiko; Zhou, Xin; Yamagami, Ayana; Onoue, Takeshi; Kawaguchi, Yohei; Miyata, Takashi; Sugiyama, Mariko; Takagi, Hiroshi; Hagiwara, Daisuke; Suga, Hidetaka; Banno, Ryoichi; Hase, Tetsunari; Morise, Masahiro; Wakahara, Keiko; Yokota, Kenji; Kato, Masashi; Nishio, Naoki; Tanaka, Chie; Miyata, Kazushi; Ogura, Atsushi; Ito, Takanori; Sawada, Tsunaki; Shimokata, Tomoya; Niimi, Kaoru; Ohka, Fumiharu; Ishigami, Masatoshi; Gotoh, Momokazu; Hashimoto, Naozumi; Saito, Ryuta; Kiyoi, Hitoshi; Kajiyama, Hiroaki; Ando, Yuichi; Hibi, Hideharu; Sone, Michihiko; Akiyama, Masashi; Kodera, Yasuhiro; Arima, Hiroshi
Source
Journal of Clinical Endocrinology & Metabolism. April 2022, Vol. 107 Issue 4, pe1620, 11 p.
Subject
Language
English
ISSN
0021-972X
Abstract
Immune checkpoint inhibitors (ICIs) have been used to treat several types of advanced malignancies. However, ICIs can cause characteristic adverse events, called immune-related adverse events (irAEs), in the lung, skin, [...]
Background: Previous studies showed that although the risk of thyroid dysfunction [thyroid immune-related adverse events (irAEs)] induced by anti-programmed cell death-1 antibodies (PD-1-Ab) was as low as 2% to 7% in patients negative for antithyroid antibodies (ATAs) at baseline, it was much higher (30%-50%) in patients positive for ATAs. However, whether a similar increase occurs with combination therapy using PD-1-Ab plus anti-cytotoxic T-lymphocyte antigen-4 antibody (CTLA-4-Ab) is unknown. Methods: A total of 451 patients with malignancies treated with PD-1-Ab, CTLA-4-Ab, or a combination of PD-1-Ab and CTLA-4-Ab (PD-1/CTLA-4-Abs) were evaluated for ATAs at baseline and for thyroid function every 6 weeks for 24 weeks after treatment initiation and then observed until the last clinical visit. Results: Of the 451 patients, 51 developed thyroid irAEs after immunotherapy [41 of 416 (9.9%) treated with PD-1-Ab, 0 of 8 (0%) treated with CTLA-4-Ab, and 10 of 27 (37.0%) treated with PD-1/CTLA-4-Abs]. The cumulative incidence of thyroid irAEs was significantly higher in patients who were positive vs negative for ATAs at baseline after both PD-1-Ab [28/87 (32.2%) vs 13/329 (4.0%), P < 0.001] and PD-1/CTLA-4-Abs [6/10 (60.0%) vs 4/17 (23.5%), P < 0.05] treatments. The risk of thyroid irAEs induced by PD-1/CTLA-4Abs, which was significantly higher than that induced by PD-1-Ab, in patients negative for ATAs at baseline was not statistically different from that induced by PD-1-Ab in patients positive for ATAs at baseline. Conclusions: This study showed that the incidence of thyroid irAEs was high and not negligible after PD-1/CTLA-4-Abs treatment even in patients negative for ATAs at baseline. Key Words: combination, CTLA-4, irAE, PD-1, thyroiditis
Background: Previous studies showed that although the risk of thyroid dysfunction [thyroid immune-related adverse events (irAEs)] induced by anti-programmed cell death-1 antibodies (PD-1-Ab) was as low as 2% to 7% in patients negative for antithyroid antibodies (ATAs) at baseline, it was much higher (30%-50%) in patients positive for ATAs. However, whether a similar increase occurs with combination therapy using PD-1-Ab plus anti-cytotoxic T-lymphocyte antigen-4 antibody (CTLA-4-Ab) is unknown. Methods: A total of 451 patients with malignancies treated with PD-1-Ab, CTLA-4-Ab, or a combination of PD-1-Ab and CTLA-4-Ab (PD-1/CTLA-4-Abs) were evaluated for ATAs at baseline and for thyroid function every 6 weeks for 24 weeks after treatment initiation and then observed until the last clinical visit. Results: Of the 451 patients, 51 developed thyroid irAEs after immunotherapy [41 of 416 (9.9%) treated with PD-1-Ab, 0 of 8 (0%) treated with CTLA-4-Ab, and 10 of 27 (37.0%) treated with PD-1/CTLA-4-Abs]. The cumulative incidence of thyroid irAEs was significantly higher in patients who were positive vs negative for ATAs at baseline after both PD-1-Ab [28/87 (32.2%) vs 13/329 (4.0%), P < 0.001] and PD-1/CTLA-4-Abs [6/10 (60.0%) vs 4/17 (23.5%), P < 0.05] treatments. The risk of thyroid irAEs induced by PD-1/CTLA-4Abs, which was significantly higher than that induced by PD-1-Ab, in patients negative for ATAs at baseline was not statistically different from that induced by PD-1-Ab in patients positive for ATAs at baseline. Conclusions: This study showed that the incidence of thyroid irAEs was high and not negligible after PD-1/CTLA-4-Abs treatment even in patients negative for ATAs at baseline. Key Words: combination, CTLA-4, irAE, PD-1, thyroiditis