僵直性脊椎炎患者使用腫瘤壞死因子抑制劑治療之藥物存活分析：台灣單一醫學中心回溯性研究

Drug Survival of Tumor Necrosis Factor-αInhibitors Among Patients with Ankylosing Spondylitis: A Single-Center Retrospective Study in Taiwan

目的：運用真實世界數據探討僵直性脊椎炎(AS)患者使用腫瘤壞死因子抑制劑(TNFi)治療的藥物存活率。
方法：本回顧性納入2016年至2022年在臺中榮民總醫院接受腫瘤壞死因子抑制劑之僵直性脊椎炎患者。分析患者的數據，以了解腫瘤壞死因子抑制劑之藥物存活和停用情況。
結果：我們納入了269名使用腫瘤壞死因子抑制劑治療的僵直性脊椎炎患者。總共37名患者更換了他們的第一線腫瘤壞死因子抑制劑的治療，包括52名恩博使用者中有4名換藥(7.7%)、132名復邁使用者中有26名換藥(19.7%)和79名欣普尼使用者中有7名換藥(8.9%)。其中，28名患者轉為使用第二線腫瘤壞死因子抑制劑，9名患者轉為白血球介素17抑制劑。接受類克(n=1)或欣膝亞(n=5)治療的患者並未換藥。每年每100人從恩博、復邁和欣普尼換藥的發生率各別為1.82、5.02和2.08。恩博、復邁和欣普尼的藥物存活三者存有顯著差異(p = 0.025)。在使用腫瘤壞死因子抑制劑治療五年內的患者中，復邁相較於恩博呈現明顯較高的換藥發生率比值(IRR=10.36)與風險比值(在單變量與多變量分析中各為HR (95% CI) = 8.76 (1.17–65.47),和HR (95% CI) = 9.66 (1.14–81.63)。牙周病在多變量分析是換藥的負預測因子[HR (95% CI) = 0.08 (0.01–0.69)]，而周邊關節炎則在單變量和多變量分析中與換藥顯著相關(分別各為HR (95% CI) = 3.00 (1.48–6.07),和HR (95% CI) = 6.27 (2.31–17.03))。
結論：復邁相較於恩博呈現較高的換藥發生趨勢，特別是在使用腫瘤壞死因子抑制劑治療的五年內。對僵直性脊椎炎患者來說，合併牙周病與腫瘤壞死因子抑制劑之藥物存活顯著相關，而合併周邊關節炎則與腫瘤壞死因子抑制劑之換藥顯著相關。

Objectives: Our study investigated the drug survival of tumor necrosis factor-αinhibitors (TNFi) among patients with ankylosing spondylitis (AS) in a real-world setting.
Methods: Patients with AS treated with TNFi from 2016 to 2022 in Taichung Veterans General Hospital were retrospectively enrolled. Data collected from patients were analyzed for drug survival and switching of TNFi.
Results: We included 269 patients with AS who received TNFi. Thirty-seven patients changed their first-line TNFi, including 4 of 52 etanercept (ETN) users (7.7%), 26 of 132 adalimumab (ADM) users (19.7%), and 7 of 79 golimumab (GLM) users (8.9%). Incidence rates of drug switching from ETN, ADM, and GLM per 100 person-years were 1.82, 5.02, and 2.08. Drug survival showed a significant difference among ETN, ADM and GLM (p = 0.025). In comparison to ETN, ADM exhibited a significant increase in IRR (10.36) and HRs, in univariable and multivariable analyses [HR (95% CI) = 8.76 (1.17–65.47) and HR (95% CI) = 9.66 (1.14–81.63)], during the first 5 years of TNFi therapy. Periodontitis was a negative predictor for drug switching in multivariable analysis [HR (95% CI) = 0.08 (0.01–0.69)], and peripheral arthritis was a positive predictor for drug switching in univariable and multivariable analyses [HR (95% CI) = 3.00 (1.48–6.07) and HR (95% CI) = 6.27 (2.31–17.03)].
Conclusion: A tendency toward more drug switching in ADM compared to ETN was observed, particularly within the first 5 years of TNFi therapy. Periodontitis was associated with drug survival, and peripheral arthritis was associated with drug switching, significantly.