生物製劑於中重度斑塊狀乾癬治療效用之回溯性病例系列研究

Evaluation of biologics in patients with moderate to severe plaque psoriasis_ retrospective case series research

林俐妏(Li-Wen Lin)

指導教授 ： 林英琦

高雄醫學大學/藥學院/藥學系碩士在職專班/碩士(2020年)

摘要

研究背景/目的:
斑塊性乾癬是一種慢性、發炎性的自體免疫疾病，其特徵為角質細胞異常分化與過度增生。目前斑塊性乾癬病人治療之方法有傳統治療(局部外用藥治療、照光治療、口服藥物治療)及生物製劑治療。目前在台灣取得健保給付的生物製劑有7項，想了解在健保條件下生物製劑使用後之臨床療效、復發的情況，作為未來藥物品項設定及藥物選擇建議之依據。

研究方法:
本研究利用回溯性研究，以南部某區域醫院2014年1月至2019年12月間中至重度斑塊性乾癬之病人為研究對象，藉由電子病歷系統、紙本病歷及健保申報資料調閱取得研究變項資料，首要探討中至重度斑塊性乾癬病人使用生物製劑後之療效評估，包含PASI平均值之改善程度、PASI-75及PASI-90的達成率，來了解生物製劑於中重度斑塊性乾癬病人之醫療利用及效益；次要探討，於2年療程後，中至重度斑塊性乾癬病人的復發情況。

研究結果:
在收錄的14位病人，使用生物製劑治療前嚴重度PASI的基礎值為21.24 ± 9.78，使用之生物製劑分別為adalimumab (n=3)、ustekinumab (n=10)及secukinumab (n=1)。
療效部分，在6個月、12個月、18個月及24個月的治療結果發現，依此時間區段的PASI平均值的改善程度為65%、76%、76%及78%；PASI-75達成率為43%、64%、57%及64%；此時間區段PASI-90達成率為14%、29%、14%、21%。依發紅、病灶厚度及脫屑狀況之嚴重度呈現，此時間區段的PASI平均值的改善程度:發紅為64%、69%、72%及78%；病灶厚度為62%、75%、76%及77%；脫屑狀況為60%、73%、74%及68%。依乾癬涉及部位(頭頸、上肢、軀幹、下肢)之嚴重度呈現，此時間區段的PASI平均值的改善程度:頭頸為67%、82%、87%及90%；上肢為61%、76%、76%及80%；軀幹為60%、69%、71%及76%；下肢為59%、67%、69%及68%。
復發部分，在12個完成2年療程的病人，有10個病人產生復發，停藥到復發間隔時間為7.50 ± 3.60 (月)。復發後再此使用生物製劑治療於6個月、12個月、18個月及24個月後其PASI值之改善度分別為72%、70%、70%、45%。

結論與建議:
雖本研究中討論之生物製劑均屬較早期機轉之藥物，但是仍發現無論使用何種生物製劑來治療中至重度斑塊性乾癬之病人，約莫都可以在6個月至12個月的療程下有顯著的改善；然在其後持續的治療至2年療程內，約莫都僅能維持最先6個月至12個月的成效，改善幅度有限；復發之病人若使用與之前治療相同之生物製劑，就目前短期零星病人之追蹤，治療後仍呈現與之前相似之療效，沒有特別觀察到藥物耐受性。
小型醫院或許受限於品項及成本支出，無法備齊所有藥物，但透過本研究之發現，可以提供部分建議供參考之
1.若6-12個月之治療，仍無達到PASI-75，可以評估是否更換不同機轉之生物製劑。(若一年的治療下沒看到成效，後續成效幾乎不明顯)
2.針對復發之病人，再使用相同生物製劑，是可行的。(因目前仍有看到治療後療效，沒有明顯之耐受性產生)
3.針對品項考量，建議若要引進採不同機轉、更多適應症之品項引進。

關鍵字

斑塊性乾癬

並列摘要

Background/Aim:
Plaque psoriasis is a chronic, inflammatory autoimmune disease, which is characterized by abnormal differentiation and hyper-proliferation of keratinocytes. The treatment for patients with plaque psoriasis include traditional treatment (topical treatment, phototherapy and traditional disease-modifying antirheumatic drugs (DMARD)) and biological treatment. For patients with moderate to severe plaque psoriasis that cannot be relived by traditional treatment for half a year, Medicare could reimburse for the use of biological agents. It is important to understand the clinical efficacy on patients with moderate to severe plaque psoriasis after the use of biological agents.

Method:
This study was a retrospective research, to search for the patients with moderate to severe plaque psoriasis and has used biological agents from January 2014 to December 2019 in a regional hospital in the southern Taiwan. The study data was collected from the electronic medical record system, paper medical record and health insurance declaration Data. The primary outcome was the percentage of mean PASI change, the achievement of PASI-75 (psoriasis area severity index-75) and the achievement of PASI-90. The secondary outcome was the occurrence of relapse.

Result:
Before treatment with biological agents, the basic value of the patient's PASI score was 21.24 ± 9.78. The biological agents used were adalimumab (n = 3), ustekinumab (n = 10) and secukinumab (n = 1).
At 6 months, 12 months, 18 months and 24 months of treatment results, it was found that the percentage of mean PASI improvement in this period were 65%, 76%, 76% and 78%; the achievement rates of PASI-75 were 43%, 64%, 57% and 64%; the achievement rates of PASI-90 were 14%, 29%, 14% and 21% respectively. According to the severity of redness, thickness and scaling, in this period the percentage of PASI improvement : redness were 64%, 69%, 72% and 78%；thickness were 62%, 75%, 76% and 77%；scaling were 60%, 73%, 74% and 78%. According to the severity of psoriasis involved parts (head and neck, upper limbs, trunk, lower limbs), in this period the percentage of PASI improvement : head and neck were 67%, 82%, 87% and 90%；upper limbs were 61%, 76%, 76% and 80%；trunk were 60%, 69%, 71% and 60%；lower limbs were 59%, 67%, 69% and 68%.
In the relapse part, among 12 patients who completed the 2-year course of biologic treatment, 10 patients had relapse psoriasis, and the interval between withdrawing the drug and relapse was 7.50 ± 3.60 (months). After relapse, the percentage of mean PASI improvement after 6 months, 12 months, 18 months, and 24 months were 72%, 70%, 70%, and 45%, respectively.

Conclusion:
This study found that no matter which biological agent was used to treat patients with moderate to severe plaque psoriasis have a significant improvement in the course of 6 months to 12 months. However, the benefits of continuous treatment (treatment until 2 years) just only maintain the first 6 to 12 months of clinical efficacy. Even when patients were treated with the same biological agent as the previous treatment after the disease relapse, the short-term sporadic follow-up of the patient still shows a similar effect to the previous treatment, and no drug tolerance was observed.
Research with data for a small-scale hospitals may be limited by items control and costs without all of the biologic agents available for clinicians to use, but through the findings of this research, some suggestions can be provided as reference:
1. If PASI-75 was not achieved after 6-12 months of treatment, it may be suggested that select another biological agent with different mechanisms might be optimal.
2. It is still efficacious to use the same biological agent for relapsed patients.
3. According to product considerations were recommended to introduce products with different mechanisms and more indications.

並列關鍵字

plaque psoriasis ； PASI-75 ； PASI-90

參考文獻

參考文獻

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