類風濕性關節炎病患使用生物製劑恩博停用藥物與事件之分析

Discontinuation and adverse events or events of Etanercept treatment in patients with rheumatoid arthritis

背景：本研究目的在探討罹患類風濕性關節炎之患者，長期使用生物製劑恩博之安全性與停用生物製劑與不良事件之相關風險因子探討。材料與方法：追蹤與分析林口長庚紀念醫院在2003年至2010年期間內，181位經健保給付使用恩博之類風濕性關節炎病患。結果：在181位接受恩博治療之類風濕性關節炎病患中有153（84.5%）位為女性。診斷平均年齡為44.8 ± 13.9歲，開始使用恩博的平均年齡為51.4 ± 13.6歲，平均使用恩博的時間為39.4 ± 27.5個月（範圍：1.4-87.0，中位數：32.6），平均用藥前DAS-28分數為6.90 ± 1.06分。在181位病患中，有34（18.8%）位在接受恩博治療過程中不良事件，其中4名發生肺結核，17名發生細菌性感染，7名發生病毒性感染，3名發生神經相關病變，2名病患腫瘤發現，並有1位可能MTX治療造成肝炎。4名肺結核病患中有一名是NTM感染之左下葉肺炎，有一名懷疑是過去左上肺葉結核的復發。此外，有一名B肝帶原者在使用後引起B肝急性發作而引發急性肝衰竭死亡。在發生不良事件的34名病患中，有16（47%）名病患因為這些不良事件而無法持續使用恩博。總計有13（7.2%）名病患因為感染合併症而無法持續使用恩博。分析顯示合併類固醇治療的病患有較高不良事件發生的可能性（OR 4.83, 95% CI 1.05-22.19, p=0.043）。另一方面，病患使用恩博前有較高的DAS-28分數（>8.0）（OR 3.20, 95% CI 1.59-6.46, p=0.001）以及治療過程中有發生不良事件的病患（OR 2.50, 95% CI 1.30-4.79, p=0.006）與恩博的中斷使用有關。結論：雖然恩博目前在治療較嚴重的類風濕性關節病患已經達到很好的療效，但在長期使用時，醫師仍須注意其潛在的感染事件，尤其合併類固醇治療之病患更需注意不良事件的發生。此外，使用恩博前較高的DAS-28分數（>8）與日後的停藥可能性較高有關聯。

Background: This study examined the long-term safety of Etanercept treatment and predictors of the discontinuation and adverse events or events of therapy in patients with rheumatoid arthritis (RA). Material and Method: Adverse events or events were recorded and analyzed for 181 consecutive RA patients followed in our department from 2003 to 2010. All enrolled patients were treated with Etanercept reimbursed by National Health Insurance. Results: A total of 181 RA patients being treated with Etanercept were enrolled, of whom 153 (84.5%) were women. The mean age at diagnosis was 44.8 ± 13.9 years, and the mean age for starting Etanercept treatment was 51.4 ± 13.6 years. The mean duration of Etanercept treatment was 39.4 ± 27.5 months (median 32.6 months; range 1.4 to 87.0 months). At baseline, the mean DAS-28 score was 6.90 ± 1.06. Of the 181 patients, 34 cases (18.8%) developed adverse events or events during the treatment period (mycobacteria in 4, bacterial infections in 17, virus infection in 7, neuropathy in 3, malignancy in 2, and other drug related event in 1). One of the tuberculosis cases with left upper lobe lung lesion was possible due to reactivation. One case had left lower lobe nontuberculous mycobacterium (NTM) pneumonia. One mortality case with hepatitis B virus carrier had hepatitis B flare up with acute liver failure. Of these 34 cases, 16 (34%) discontinued Etanercept treatment. Concomitant treatment with corticosteroid increased the risk of adverse events or events (OR 4.83, 95% CI 1.05-22.19, p=0.043). Patients with an initial DAS-28 score greater than 8.0 (OR 3.20, 95% CI 1.59-6.46, p=0.001) and patients who experienced adverse events or events (OR 2.50, 95% CI 1.30-4.79, p=0.006) were more likely to discontinue Etanercept treatment. Conclusion: Despite the good clinical efficacy of Etanercept treatment, physicians must remain alert for adverse events or events in patients treated with this medication. Extra vigilance is required when treating patients with a combination of Etanercept and corticosteroid. Patients who had initial DAS-28 scores more than 8.0 were more likely to discontinue Etanercept treatment.