作者：Laurie Barclay, MD
出處：WebMD醫學新聞
December 1, 2008 — 根據線上發表於11月17日且將於12月印行的Pediatrics期刊中的第二期隨機試驗結果，每週使用tacrolimus藥膏三次，可以降低穩定型異位性皮膚炎(atopic dermatitis，AD)的復發風險。
西北大學Feinberg醫學院/兒童紀念醫院的Amy S. Paller醫師與美國Tacrolimus藥膏研究小組的同僚表示，長期安全有效的治療選項，對於控制AD的慢性復發，以改善病患的生活品質來說相當重要；為了盡量減少持續使用皮質類固醇的風險與減少發作風險，我們檢測了運用短期外用皮質類固醇後，使用長期間歇性非類固醇tacrolimus藥膏對於原本皮膚炎發炎病灶的安全性與有效性。
病患年紀為2至15歲，有中到重度AD，隨機雙盲分派接受四天、每天兩次的alclometasone藥膏0.05%，或者tacrolimus藥膏0.03% (第一期急性期)，之後是16週的每天兩次的開放標籤tacrolimus藥膏0.03% (第一期短期)；在第二期中，這些病患中病情穩定者，再度隨機雙盲指派接受每週三天、每天一次的tacrolimus藥膏0.03%，或者無藥效的安慰劑，運用於臨床正常外觀的皮膚達40週；試驗中不可以使用皮質類固醇。
隨機分派的206名病患中，152人完成第一期，其中105 人隨機分派接受第二期(68人接受Tacrolimus藥膏，37人接受安慰劑)。在第一期中，alclometasone藥膏和tacrolimus藥膏的不良反應沒有差異，第二期中，tacrolimus藥膏和安慰劑之間的副作用也無差異。急性期時，alclometasone者的AD徵兆改善較多。之後，當所有病患短期使用tacrolimus藥膏時，並未發現有差異。相較於安慰劑組病患，第二期時以tacrolimus治療的病患顯著有較多的無病期間，出現第一次復發的間隔顯著較長，以及疾病復發的日子顯著較少。
研究作者寫道，對於穩定型中到重度AD的病患，長期間運用tacrolimus藥膏於正常外觀皮膚而非先前的病灶處，在維持疾病穩定上顯然比安慰劑更有效，且安全資料和安慰劑相當。將局部calcineurin抑制劑併入包括了臨床實務上經常使用的局部皮質類固醇之替換治療計畫中，我們發現皮質類固醇的初步治療提供了小兒中到重度AD病患症狀的早期緩解，我們的發現證實目前在AD早期治療的臨床實務，且提供對於穩定型中到重度AD病患的長期疾病控制的策略。
Astellas Pharma US, Inc支持本研究且雇用了其中兩名作者，與其他四名作者有財經關係，其中兩人也與Novartis Pharmaceuticals Corp有財經關係。
Tacrolimus Ointment May Reduce Relapse Risk for Stabilized Atopic Dermatitis
By Laurie Barclay, MD
Medscape Medical News
December 1, 2008 — Using tacrolimus ointment 3 times weekly was associated with reduced risk for relapse of stabilized atopic dermatitis (AD), according to the results of a 2-phase randomized trial published online November 17 and in the December print issue of Pediatrics.
"Long-term, safe and effective therapeutic options for managing the chronic relapsing nature of [AD] are essential for improving patient quality of life," write Amy S. Paller, MD, from Northwestern University's Feinberg Medical School/Children's Memorial Hospital in Chicago, Illinois, and colleagues from the US Tacrolimus Ointment Study Group. "To minimize the risks of continued topical corticosteroid usage and potentially reduce the incidence of flares, we tested the efficacy and safety of a rotational paradigm of initial brief application of topical corticosteroid followed by long-term intermittent application of non-steroidal tacrolimus ointment to previously inflamed sites of dermatitis."
Patients aged 2 to 15 years with moderate to severe AD were randomly assigned to 4 days of twice-daily double-blind treatment with either alclometasone ointment 0.05% or tacrolimus ointment 0.03% (phase 1 acute), followed by up to 16 weeks of twice-daily open-label tacrolimus ointment 0.03% (phase 1 short-term). In phase 2, those patients in whom disease stabilized were again randomly assigned to receive double-blind tacrolimus ointment 0.03% or vehicle applied once daily, 3 times per week, to clinically normal-appearing skin for up to 40 weeks. Corticosteroid use was not permitted during the trial.
Of 206 patients who were randomized, 152 completed phase 1, and 105 of these patients were randomly assigned to phase 2 (68 received tacrolimus ointment and 37 received vehicle). In phase 1, adverse events were not different between alclometasone and tacrolimus, nor were they different between tacrolimus and vehicle in phase 2. AD signs and symptoms were more improved with alclometasone in the acute period. Thereafter, when all patients applied tacrolimus ointment short term, no differences were observed. Compared with vehicle-treated patients, tacrolimus-treated patients in phase 2 had significantly more disease-free days, significantly longer time to first relapse, and significantly fewer disease relapse days.
"For patients with stabilized moderate to severe [AD], long-term intermittent application of tacrolimus ointment to normal-appearing but previously affected skin was significantly more effective than vehicle at maintaining disease stabilization, with a safety profile similar to vehicle," the study authors write. "Incorporating [topical calcineurin inhibitor]s into a rotational treatment plan that includes topical corticosteroids occurs routinely in clinical practice, and we found that initial treatment with a corticosteroid provides significantly better early relief of the signs and symptoms of AD in pediatric patients with moderate to severe AD than tacrolimus ointment.... Our findings substantiate current clinical practice in the early treatment of AD and provide additional insight into a long-term strategy of disease control for pediatric patients with stabilized moderate to severe AD."
Astellas Pharma US, Inc, supported this study, employs 2 of its authors, and has financial relationships with 4 other authors, 2 of whom also have financial relationships with Novartis Pharmaceuticals Corp.
Pediatrics. 2008;122;e1210–e1218. Article
[ 本帖最後由 goodcat1111 於 2008-12-15 13:05 編輯 ] |
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