痤瘡治療共識小組專家委員會議 systemic isotretinoin · isotretinoin •the only...
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痤瘡治療共識小組專家委員會議
Systemic isotretinoin
高雄榮總魏楷哲
感謝楊麗珍醫師指導、提供臨床教育資料
健保給付規定
• Isotretinoin口服製劑 (如Roaccutane):(86/9/1、87/4/1、94/3/1)
• 1.限皮膚科專科醫師使用。
• 2.需檢附病人之服藥同意書 (詳附表十),以及經傳統治療無效之病歷資料或治療前之照片,經事前審查核准後使用。
• 3.每次申請以一療程為限,若需再次療程,請檢附原來照片與最近照片再次申請事前審查核准後使用(每一療程最高總劑量為100 mg –120 mg/kg,於四至六個月完成)。
服用同意書
Isotretinoin
• The only therapy for acne that is capable of inducing remission after an adequate course of therapy is completed
• Isotretinoin與血漿蛋白質高度結合,主要為白蛋白(≧99.9%)
• 原藥最終排除半衰期平均為19小時,4-oxo-isotretinoin的最終排除半衰期較長,平均為29小時。
How Isotretinoin works
shrinkage of sebaceous glands
inhibition of the sebum-dependent bacterium Propionibacterium acnes
fostering keratinocyte differentiation and by normalizing desquamation
Isotretinoin 治療痤瘡:近年國際上的建議規範
地點 出處 年度 適應症 建議劑量
European Evidence-Based Guidelines for Treatment of Acne S3
Journal of the European Academy of Dermatology and Venereology
(2012) severe papulopustularor conglobate acne
100–120 mg/kg
American Academy of Dermatology
Journal of the American Academy of Dermatology
(2007)(新版:預計2015)
Severe recalcitrant nodular acne
cumulative dose of 120–150mg/kg
Consensus on Evidence-Based Practice in Acne (Asian Working Group)
The Journal of Dermatology
(2011) Not conclusive
建議適應症
• 囊腫型痤瘡(acne cystica)或結節型痤瘡(nodular acne)
• 嚴重型且難控制的發炎性痤瘡 (severe nodular and recalcitrant inflammatory acne)– Treatment-resistant acne
• Scarring acne, severe
• Acne causing significant psychological distress
• Antibiotic-induced gram-negative folliculitis in patients with acne vulgaris
其他適應症
• Acne fulminans
The treatment of acne fulminans: a review of 25 cases.Br J Dermatol. 1999;141(2):307.
Acne fulminans: report of clinical findings and treatment of twenty-four patients. J Am Acad Dermatol. 1993;28(4):572.
J Eur Acad Dermatol Venereol. 2011 May;25(5):501-7.
不同劑量的療效與復發率
J Clin Aesthet Dermatol. 2014 Feb;7(2 Suppl):S3-S21.The use of isotretinoin in the treatment of acne vulgaris: clinical considerations and future directions.
J Am Acad Dermatol. 2007;56(4):651.
J Am Acad Dermatol. 2006;54(4):644Low-dose isotretinoin in the treatment of acne vulgaris.
建議劑量
• FDA: starting daily dose is 0.5mg/kg/day, which is increased to l mg/kg/day, as tolerated
- 0.5mg/kg/day to 2.0mg/kg/day
- Once or twice daily for 15 to 20 weeks
- (QD vs. BID is not studied)
• Cumulative dose: >120 to 150mg/kg if isotretinoin is administered over the maximum duration of treatment (20 weeks [5 months]) indicated in the FDA-approved package inserts.
現實生活中使用isotretinoin持續治療時間:
J Clin Aesthet Dermatol. 2014 Feb;7(2 Suppl):S3-S21.
(20週)
口服isotretinoin停藥後,Acne復發的機會:
Actas Dermosifiliogr. 2013 Jan;104(1):61-6. Acne relapse rate and predictors of relapse following treatment with oral isotretinoin.
復發機會高,復發比例差異極大,但是機會隨著追蹤時間拉長而增加
口服isotretinoin停藥後,影響Acne復發的可能因素
Actas Dermosifiliogr. 2013 Jan;104(1):61-6. Acne relapse rate and predictors of relapse following treatment with oral isotretinoin.
高劑量是否會有比較好的療效呢?Higher dose for isotretinoin
• 高劑量的療效是否較好?
• 停藥後復發的機會是否減少?
• 副作用的機會是否增加? (Benefit vs. Risk)
• lower-dose vs. high dose: <220 mg/kg vs. > 220 mg/kg
• The rate of relapse: 43.8% (95% CI, 16.3%-40.3%) vs. 26.6% (24.1%-65.7%) (P = .22)
From: High-Dose Isotretinoin Treatment and the Rate of Retrial, Relapse, and Adverse Effects in Patients With
Acne Vulgaris
JAMA Dermatol. 2013;149(12):1392-1398. N=78, with comparison 74.1% were white people.
From: High-dose isotretinoin in acne vulgaris: improved treatment outcomes and quality of life.
Int J Dermatol. 2012 Sep, 51(9):1123-30 cumulative dose:290 mg/kg. USA. N=80, no comparison group.
From: High-Dose Isotretinoin Treatment and the Rate of Retrial, Relapse, and Adverse Effects in Patients With
Acne Vulgaris
JAMA Dermatol. 2013;149(12):1392-1398.
From: High-Dose Isotretinoin Treatment and the Rate of Retrial, Relapse, and Adverse Effects in Patients With
Acne Vulgaris
JAMA Dermatol. 2013;149(12):1392-1398. doi:10.1001/jamadermatol.2013.6746
低劑量是否會真的療效比較差呢?Lower dose of isotretinoin for acne
• 藥物的反應是否有人種差異?
• 多低的劑量算是低劑量呢?
Indian J Dermatol. 2014 May;59(3):316. Safety and efficacy of low-dose isotretinoin in the treatment of moderate to severe acne vulgaris.
20 mg QD for 3 months
Fifty cases. India
Indian J Dermatol. 2014 May;59(3):316. Safety and efficacy of low-dose isotretinoin in the treatment of moderate to severe acne vulgaris.
低劑量的起始療效不會比較不好。但是復發率呢?
J Am Acad Dermatol. 2001 Aug;45(2):187-95.
Israel.
J Am Acad Dermatol. 2006 Apr;54(4):644-6.
Follow: 4 yrs
Arch Dermatol Res. 2007 Dec;299(10):467-73.
Turkey.Follow: 12 mo
India. Follow: 6mo
J Eur Acad Dermatol Venereol. 2009 May;23(5):556-60
建議禁忌症
• 禁止使用於懷孕孕婦或在治療期間可能懷孕的婦女:使用前一個月,使用期間,使用後一個月,都要完全避孕
• 肝功能不全或異常• 維生素A過多症• 血脂值過高的病患
• 已知對本藥和其任何成分過敏者peanut oil? Paraben敏感?
• 飛行員,以及需要敏銳夜間視力者
24
Isotretinoin in pregnancy
• labeling: pregnancy category X
• Increased risk of spontaneous abortion and premature birth
• Congenital malformations: craniofacial, cardiac, thymus, CNS28% of exposed pregnancies affected at birth
iPLEDGE
teratogen
• Risk management
• But what should we do if exposure or unexpected pregnancy happens?
- spontaneous abortion, malformation?
- or nothing?
副作用、後遺症
Predictable:• 皮膚:唇炎,發疹,皮膚乾燥,對光敏感• 耳鼻喉︰鼻出血、鼻乾燥• 血液:血清中三酸甘油脂濃度增加50%~70%
Unpredictable:• 中樞神經:頭痛,倦感• 口服A酸後,發生良性顱內高血壓(pseudo-tumor
cerebri)• 肝臟:SGOT,SGPT,鹼性磷酯酶上昇• 貧血,血小板增多
JAMA Dermatol. 2013;149(12):1392-1398. doi:10.1001/jamadermatol.2013.6746
JAMA Dermatol. 2013;149(12):1392-1398. doi:10.1001/jamadermatol.2013.6746
追蹤
• Triglycerides, Cholesterol, Transaminase, Complete blood counts
• 應於治療前及開始服藥4-6週後檢查,然後每3個月檢查一次。
• Hyperostosis, premature epiphyseal closure, bone demineralization.
– routine screen is not required. (JAAD)
• Mood disorder: not routine required.
目前有爭議的幾個問題
Psychosocial “Complications”
of acne
Depression
Anxiety
Social withdrawal
Poor self esteem
Suicide ideation
Overall quality of life
Isotretinoin increases the risk of inflammatory bowel disease?
• 一年內發生潰瘍性結腸炎的機率將會比未服用者,高出四倍?
• 真的是如此嗎?
Am J Gastroenterol. 2014 Apr;109(4):563-9.Isotretinoin and risk of inflammatory bowel disease: a French nationwide study.
J Invest Dermatol. 2013 Apr;133(4):907-12.Isotretinoin use and the risk of inflammatory bowel disease: a population-based cohort study.
Am J Gastroenterol. 2006 Jul;101(7):1569-73.Possible association between isotretinoin and inflammatory bowel disease.
From: Isotretinoin Exposure and Risk of Inflammatory Bowel Disease
JAMA Dermatol. 2014;150(12):1322-1326. doi:10.1001/jamadermatol.2014.1540
Isotretinoin 和嚴重的疤痕增生
• 可能造成無法預期的組織修復作用,讓傷口癒合不良,有可能造成疤痕形成,例如肥厚性疤痕或蟹足腫,所以進行磨皮雷射或侵入性治療、手術後,建議避免使用A酸。若正在進行口服A酸療程,也應停藥「一段時間」才能進行磨皮或侵入性治療。
• J Am Acad Dermatol. 1986 Aug;15(2 Pt 1):280-5.• Br J Dermatol. 1988 May;118(5):703-6. • J Am Acad Dermatol. 1994 May;30(5 Pt 2):852-3.
Dermabrasion for acne scars during treatment with oral isotretinoin.Dermatol Surg. 2010 Apr;36(4):483-9.
Early chemabrasion for acne scars after treatment with oral isotretinoin.Dermatol Surg. 2012 Sep;38(9):1521-6.)
Safety of performing invasive acne scar treatment and laser hair removal in patients on oral isotretinoin: a retrospective study of 110 patients.Int J Dermatol. 2014 Oct;53(10):1281-5.
Isotretinoin不會引起嚴重的疤痕增生