Alitretinoin改善反應不佳慢性手部皮膚炎症狀


  Dec. 20, 2004 - 一項發表於12月號皮膚學學誌的多中心、隨機分派、雙盲、安慰劑控制前瞻試驗結果顯示,每天使用alitretinoin可以誘發53%中度至嚴重之對標準局部療法反應不佳慢性手部皮膚炎(CHaD)症狀病患的臨床反應,而且可以降低疾病的病徵與症狀達70%。
  
  德國Heinrich-Heine大學醫院皮膚科Thomas Ruzicka醫師與其同事表示,輕微的CHaD通常對於潤滑劑與局部類固醇有足夠的反應,但是如果對標準療程反應不佳,更嚴重的病患可能會日漸衰弱;研究人員附帶表示,使用非標準療法(口服類固醇、cyclosporine、acitretin、psoralen-UV-A與放射線療法)通常因為副作用或是不便而受限。
  
  為了要評估alitretinoin(BAL4079;Basilea藥廠)的療效,研究人員收納了319位對標準療法反應不佳的CHaD病患,這些病患被隨機分派接受每天3次的alitretinoin(每天10、20、40毫克)或是安慰劑達12週,在試驗結束前以及後3個月進行評估。
  
  療效評估項目包括醫師對CHaD嚴重度的整體評估(PGA)、對病患病況進展的全身評估(PaGA)、以及總病灶症狀指數(TLSS);當病患的PGA評為清除時(沒有殘留肉眼可見的皮膚炎)或是幾乎清除(少許紅腫以及/或是結痂)都被認定為有療效。
  
  Alitretinoin,相較於安慰劑,被發現對於PGA分數有明顯且與劑量相關的作用(P<.001);10、20以及40毫克劑量的反應率分別為39%、41%與53%,而且全部都達到統計上的差異(分別為P=.01,P=.002與P<.001)。
  
  所有形式的CHaD(過度角質化、指尖濕疹、起泡),以及之前對所有療法都沒有反應的病患均有反應。
  
  TLSS指數從基準點到試驗後的進步,不論是何種劑量的alitretinoin,相較於安慰劑都達到統計上的差異(P<.001),而且效果是與劑量相關的(P<.001);每天服用10毫克病患的TLSS指數,相較於基準點下降了59%(95%信賴區間為33%到73%),每天服用20毫克病患的下降52%(95%信賴區間為42%到73%),每天服用40毫克病患的下降70.5%(95%信賴區間為44%到80%)。
  
  病患對於治療的耐受性大致良好,每天服用10、20、40毫克劑量病患發生副作用的比率,與安慰劑組相差不多;每天服用40毫克劑量發生的副作用,包括頭痛、面部潮紅、血脂肪濃度上升、血紅素值些微下降、以及游離甲狀腺素濃度下降。
  
  而一開始就有反應的病患中,26%在3個月的追蹤期中需要處方治療他們的CHaD,而且被認為是疾病再發;疾病再發率在服用每一種劑量的病患之間都是差不多的。
  
  在這項試驗中,口服alitretinoin對於大部分對標準療法反應不佳的中度或是重度CHaD病患,可以引發臨床上明顯的反應;研究人員的結論是,這項試驗令人興奮的發現支持了使alitretinoin在未來的試驗中治療CHaD病患的潛力。
  
  這項試驗由alitretinoin製造廠商,Basilea藥廠贊助;研究人員個人有接受這家公司的研究經費以及/或是受雇於這家公司。

Alitretinoin Improves Symptoms

By Yael Waknine
Medscape Medical News

Dec. 20, 2004 — A daily regimen of oral alitretinoin induces clinical responses in up to 53% of patients with moderate to severe chronic hand dermatitis (CHaD) that is refractory to standard topical therapy, and it reduces the signs and symptoms of the disease by up to 70%, according to the results of a multicenter, randomized, double-blind, placebo-controlled prospective study published in the December issue of the Archives of Dermatology.

"Mild cases of CHaD are usually adequately responsive to emollients and topical corticosteroids, but the disease can be debilitating in patients with more severe disease if they are refractory to this standard regimen," write Thomas Ruzicka, MD, from the Department of Dermatology at Heinrich-Heine University Hospital in Dusseldorf, Germany, and colleagues, noting that use of nonstandard therapies (oral corticosteroids, cyclosporine, acitretin, psoralen-UV-A, and radiotherapy) is often limited by adverse effects or inconvenience.

To evaluate the safety and efficacy of alitretinoin (BAL4079; Basilea Pharmaceutica Ltd.), the investigators recruited 319 patients with CHaD refractory to standard topical therapy. Patients were randomized to receive one of three daily doses of alitretinoin (10 mg/day, 20 mg/day, 40 mg/day) or placebo for 12 weeks. Assessments were performed at the end of the trial and at a three-month follow-up.

Efficacy measures included the physician's global assessment (PGA) of overall CHaD severity, the patient's global assessment (PaGA) of improvement, and the total lesion symptom score (TLSS). Patients with PGA ratings of clear (no residual visible dermatitis) or almost-clear (minimal erythema and/or scaling) were considered responders.

Alitretinoin was found to have a significant and dose-dependent effect on PGA scores (P < .001) compared with placebo. Response rates of 39%, 41%, and 53% corresponded to 10-, 20-, and 40-mg doses, respectively (placebo, 27%).

The authors attribute the response rate observed in the placebo group to spontaneous variability that may be more common in patients with less severe disease.

PaGA scores revealed a similar pattern; response rates of 29%, 34%, and 43% corresponded with 10-, 20-, and 40-mg doses of alitretinoin and all were significant compared with placebo (P = .01, P = .002, and P < .001, respectively).

Responses were observed for all types of CHaD (hyperkeratotic and fingertip eczema, pompholox) and in those previously unresponsive to all therapies.

Improvements in TLSS scores from baseline were significantly greater with all doses of alitretinoin compared with placebo (P < .001), and the effect was dose-dependent (P < .001). TLSS scores improved compared with baseline by 59% in the 10-mg/day group (95% confidence interval [CI], 33% - 73%), by 52% in the 20-mg/day group (95% CI, 42% - 73%), and by 70.5% in the 40-mg/day group (95% CI, 44% - 80%).

Treatment was generally well tolerated, with similar adverse event rates among the placebo and 10- and 20-mg dose groups. Adverse events with the 40-mg/day dose included headache, flushing, elevations in serum lipid levels, slightly decreased hemoglobin level, and decreased free thyroxin level.

Of the initial responders, 26% required prescription therapy for their CHaD during the three-month follow-up period and were considered to have relapsed. Rates of relapse were similar in all dose groups.

"In this study, oral alitretinoin induced clinically significant responses in a high percentage of patients with moderate or severe CHaD refractory to standard topical therapy," the authors conclude. "The encouraging results of this trial support further clinical studies of alitretinoin in the treatment of patients with CHaD."

The study was supported by Basilea Pharmaceutica Ltd., the maker of alitretinoin. Individual investigators report receiving grants or consultancy fees from and/or are employed with the company.

Arch Dermatol. 2004;140:1453-1459

Reviewed by Gary D. Vogin, MD

    
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