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作者：Deborah Brauser  
出處：WebMD醫學新聞

　　March 9, 2010 (佛州邁阿密海灘) — 根據發表於美國皮膚科學院第68屆年會PSUNRISE研究結果，輕微到嚴重斑塊型乾癬病患，在對etanercept (商品名Enbrel，Amgen與Wyeth藥廠)治療反應不佳之後改用infliximab (商品名Remicade，Centocor Ortho Biotech公司)，可以降低疾病活性。
　　
　　第一作者、Tufts大學醫學院、Tufts醫學中心皮膚科主任Alice Gottlieb博士表示，本研究的目的是，探討對於使用一種腫瘤壞死因子阻斷劑(TNF-阻斷劑)etanercept失敗的病患，改用另一種TNF-阻斷劑infliximab是否可以緩解。
　　
　　她報告指出，這很重要，因為乾癬病患一般從年輕發病之後，終身都會受到影響，雖然TNF是不錯的標靶，但是並非每個人都適用某種TNF阻斷劑，有些病患可能會沒有反應，因此，就病患一生而言，得有多種TNF阻斷劑供他們選擇。
　　
　　她指出，這不是一個比較試驗，etanercept和infliximab都是不錯的藥物，而本研究目的不在於比較。
　　
　　【探討疾病活性與生活品質】
　　研究者納入215名18歲以上病患(63.7%為男性；平均年紀44.4歲)、有明顯的疾病活性(定義為固定醫師整體評估[PGA]分數大於等於2)，之前曾經接受etanercept 25 mg 每週兩次或者50 mg 每週一次或兩次，單獨使用或者還併用methotrexate或cyclosporine，治療至少4個月但治療反應不足，這些病患在使用最後一劑的etanercept之後(第0週)，開始接受劑量為5 mg/kg的infliximab輸注2週；然後在第2、6、14與22週重複輸注。
　　
　　在各時間點進行效果評估，直到第26週，初級終點為第10週時達到PGA分數小於等於1的病患人數百分比，開始時的PGA中位數為2.8。
　　
　　次級終點包括分析身體表面積(BSA)、乾癬區域與嚴重度指數(PASI)分數與反應、測量健康相關生活品質、乾癬情況評量等，安全性評估則進行到第30週。
　　
　　Gottlieb博士解釋，此外，當前105名病患完成10週試驗時，進行安全性的期中分析，結果在之前已經發表。
　　
　　【使用Infliximab有快速而持久的反應】
　　第10週時，使用infliximab治療的共有65.4%，其PGA分數為清除(0分)或輕微(1分)，26週時，此比率增加到72.4%，在第10週和第26週的PASI 75反應比率分別是51.7%和54.5%。
　　
　　Gottlieb博士報告指出，多數在治療開始的6週內出現PGA反應，所以，我們不只緩解了65%的病患，而且是相當迅速的緩解。
　　
　　此外，Gottlieb博士報告指出，整個研究期間，平均BSA與平均DLQI [皮膚科生活品質指標]皆有持續改善，第10週時，達到DLQI小於等於1的病患百分比為44%，第26週時為41%。
　　
　　接受infliximab治療的215名病患中，5.6%發生輸注反應，68.8%有至少一種副作用，不過，只有3.7%發生一種以上的嚴重副作用。
　　
　　Gottlieb博士解釋，安全性資料就像一般的infliximab使用上所見，感染方面副作用主要是呼吸道和表皮感染有關。
　　
　　當被問到為何醫師不一開始就使用infliximab時，Gottlieb博士表示，雖然她相信它可以有最佳反應，但是並非所有病患都適合靜脈輸注。
　　
　　她結論表示，總結來說，病患可能使用etanercept但無反應，而這些無反應者中有三分之二可以使用infliximab並有迅速反應，此外，安全資料是在預期範圍內。
　　
　　【外界引述】
　　德州達拉斯Baylor研究中心乾癬研究主任、國際乾癬團體發起人Alan Menter醫師表示，這是個有趣的研究。
　　
　　未參與該研究的Menter醫師表示，所有藥廠現在都在觀察，當病患對一種治療失敗時，對同類的其他治療是否也較可能失敗，這也是本研究的焦點。
　　
　　他們探討那些對etanercept反應不佳的病患，讓他們接受類似作用的另一種藥物，雖然它是不同的抗體，結果發現，超過64%有反應，不是整類的TNF受體效應、其中一個失敗不代表所有都會失敗。
　　
　　他指出，我們期待看到更多這種研究，特別是有關新型的介白素12/23藥物，如ustekinumab。
　　
　　Centocor Ortho Biotech Services公司贊助本研究。Gottlieb博士報告擔任許多乾癬相關團體的諮詢委員， Menter醫師報告參與許多藥廠的乾癬治療研究。
　　
　　美國皮膚科學院(AAD)第68屆年會：摘要P3341。發表於2010年3月7日。


Infliximab Reduces Psoriasis Activity in Etanercept-Resistant Patients

By Deborah Brauser
Medscape Medical News

March 9, 2010 (Miami Beach, Florida) — Patients with mild to severe plaque psoriasis who switched to infliximab (Remicade, Centocor Ortho Biotech) after a poor response to etanercept (Enbrel, Amgen and Wyeth) therapy showed a reduction in disease activity, according to results from the new PSUNRISE study presented here at the American Academy of Dermatology 68th Annual Meeting.

"The purpose of this study was to see if patients who had failed one [tumor necrosis factor] TNF-blocker, etanercept, [could be rescued] with a second TNF-blocker, infliximab," said lead author Alice Gottlieb, MD, PhD, chief and chair of the dermatology department at Tufts Medical Center and Tufts University School of Medicine in Boston, Massachusetts.

"That's important because psoriasis patients have their disease generally from a young age through the rest of their lives," she reported. "Although TNF is a very good target, not everybody responds optimally to [a TNF blocker], or they lose responsiveness to one. So over a patient's lifetime, you need multiple TNF blockers to give them a choice."

She noted that this wasn't a comparison trial. "Both etanercept and infliximab are good drugs. This study wasn't about that."

Disease Activity, Quality of Life Measured

The investigators enrolled 215 patients over the age of 18 (63.7% male; mean age, 44.4 years) with "significant disease activity" (defined as a static Physician Global Assessment [PGA] score of 2 or higher) who had previously received etanercept 25?mg twice weekly or 50?mg once or twice a week, alone or with methotrexate or cyclosporine, for a minimum of 4 months, with an inadequate treatment response. These patients began receiving 5?mg/kg infusions of infliximab 2 weeks after taking their last dose of etanercept (week?0); infusions were repeated at weeks 2, 6, 14, and 22.

Efficacy evaluations were performed at all time points through to week?26, and the primary end point was the percent of patients achieving PGA scores of 1 or below at week?10. The median PGA at baseline was 2.8.

Secondary end points included analyses of body surface area (BSA), Psoriasis Area and Severity Index (PASI) scores and responses, health-related quality-of-life measures, and psoriasis assessments. Safety evaluations were given through to week?30.

In addition, "a protocol-stipulated interim analysis for safety was performed when the first 105 patients completed week?10, which has been previously reported," explained Dr. Gottlieb.

Fast, Durable Response With Infliximab

At week?10, a total of 65.4% of the patients treated with infliximab had a PGA of clear (score of 0) or mild (score of 1). At week?26, this number increased to 72.4%. PASI?75 responses at weeks?10 and 26 were 51.7% and 54.5%, respectively.

"The majority of the PGA responders exhibited this response within 6 weeks of treatment initiation," reported Dr. Gottlieb. "So not only did we rescue 65% of them, we rescued them relatively quickly."

In addition, "substantial improvements in mean BSA and mean [Dermatology Life Quality Index] DLQI were observed throughout the study," reported Dr. Gottlieb. "The proportion of patients achieving a DLQI of 1 or less was 44% at week?10 and 41% at week?26."

Of the 215 patients who received infliximab treatment, 5.6% had infusion reactions and 68.8% had at least 1 adverse event. However, only 3.7% experienced 1 or more serious adverse events.

"There was a similar safety profile to what you normally see with infliximab. Infection adverse events were primarily related to respiratory tract complaints and cutaneous infections," explained Dr. Gottlieb.

When asked why clinicians shouldn't just start treatment with infliximab, Dr. Gottlieb said that although she believes it gives the best response, "it is given by [intravenous] infusion, which is not for everyone."

"In summary, one can take etanercept nonresponders and rescue two thirds of them with infliximab and the response is quick. Plus, the safety profile is to be expected," she concluded.

Outside Quotes

"This study was interesting," said Alan Menter, MD, chair of psoriasis research at Baylor Research Institute in Dallas, Texas, and founder of the International Psoriasis Group.

"All the companies are now looking to see, when a patient has failed 1 of the treatments, [whether they are] more likely to fail another treatment in the same class. That is what this research looked at," said Dr. Menter, who was not involved with the study.

"They took those patients who did not do well on [etanercept] and put them on a drug with a similar action, even though it was a different antibody, [and found] that over 64% did respond. It isn't a class effect of TNF [receptor] that if you fail 1 you're going to fail them all."

He noted that "we're going to see more of these types of studies," especially with the new [interleukin]12/23 drugs, such as ustekinumab.

This study was sponsored by Centocor Ortho Biotech Services. Dr. Gottlieb reports sitting on the advisory boards for "many psoriasis-interested parties." Dr. Menter reports doing studies for many of the companies involved with psoriasis therapies.

American Academy of Dermatology (AAD) 68th Annual Meeting: Abstract?P3341. Presented March?7, 2010.