tiok0080 2010-5-7 14:14
數據顯示boceprevir使用於C型肝炎患者效果持續
作者：Thomas R. Collins
出處：WebMD醫學新聞
April 19, 2010 （奧地利維也納）－Boceprevir，一種研究中用於治療C型肝炎病毒（HCV）感染的口服蛋白酶抑制劑，於歐洲肝臟研究學會（EASL）第45屆年會上有額外令人激勵的研究結果發表。新研究數據顯示，病患在後續追蹤的2年間仍然維持持續病毒反應（SVR）。
根據發表於EASL年會的研究結果，以及在絲氨酸蛋白酶抑制劑治療1（SPRINT-1）研究中，在一開始的24週試驗期間，並沒有發生嚴重不良反應（SAEs）。
然而，新研究結果顯示，在轉變成野生型病毒的過程中，有部分突變是緩慢的。
這個由先靈葆雅藥廠研發的藥物，該公司於2009年11月與默克藥廠合併，目前在進行第三期臨床研究病患收納。默克藥廠高層期待在今年下半年將資料呈交食品藥物管理局，他們希望這個藥物可以在2011年核准上市。
默克藥廠高層希望新研究結果可以加強他們這件申請案。
在這項研究中擔任要職的德州休士頓貝勒醫學院肝臟部門主任John Vierling醫師表示，他們在數年前確實給了我們一些訊息，在快速追蹤案下，他們將看起來是順利的。
Vierling醫師表示，SVR是否同樣地清楚且持續？在這裡，這是持續的。是否有任何潛在的SAE？這個問題的答案是否…這些是新的藥物。我們知道治療時反應且我們知道有關SVR的資訊，但是確認沒有造成任何傷害的潛在可能，我認為這是個重要的安全觀點。
SPRINT-1研究的結果在去年的EASL會議上揭露，包括HCV基因型第一型病患報告中最好的SVR反應率。
那些使用perinterferon alfa-2b（每週15 μg/kg）與ribavirin（每天800-1400 mg，根據體重決定劑量），之後使用boceprevir（800 mg每天使用三次），達到SVR比例為75%，幾乎是未使用boceprevir控制組的2倍。
這項新研究中，研究者們追蹤那些在SPRINT-1研究中有或是未達到SVR患者，且追蹤來自兩項較小型研究中沒有反應的病患。
他們發現，在SPRINT-1研究中，24週後達到SVR的患者，相較於21位來自另外一項研究的病患，沒有任何1位再發。
290位SPRINT-1研究中的病患，有1位因為病毒發生新的突變被再度感染。研究團隊並不認為這是再發。
Vierling醫師的團隊也追蹤那些發生突變患者的病毒，轉變成野生型的過程。他們發現那些有V36M突變的患者，91%反轉，相較於R155K與T54突變型較低的反轉率，反轉為野生型的機率分別為71%與62%。
EASL的副秘書長、英格蘭倫敦皇家學院Mark Thursz醫師表示，根據過去使用boceprevir的發現，這項研究中的SVR與SAE數據並非意料之外。
他指出，這並不是最令人興奮的數據，但仍是吸引人的。
他表示，病毒突變緩慢反轉的現象是令人困擾的。
Thursz醫師表示，我們擔心的是他們轉變為野生型的過程有多緩慢，以及你停止治療後數個月內你仍然會偵測到造成抗藥性的突變。這項研究的意義是，我們不該不當地使用這些蛋白酶抑制劑。
我們必須非常確認，一旦你開始治療，你將開始清除病毒，因此你給了病患清除病毒最佳的機會。Thursz醫師進一步表示，除此之外，不適當地使用會引發突變，這可能損害到未來蛋白酶標靶藥物的使用。
這項研究接受默克藥廠的商業贊助。Thursz醫師是這項研究其中一位研究者。Thursz醫師表示沒有相關資金上的往來。
Boceprevir Hepatitis C Patients Continue to Fare Well, Data Show
By Thomas R. Collins
Medscape Medical News
April 19, 2010 (Orlando, Florida) — Contrary to conventional thought, acquired nonaccommodative esotropia (ANAET) is common and not associated with the presence of intracranial lesions, according to a new retrospective study that followed up almost 200 patients diagnosed as having the disorder for an average of 11 years.
The results were presented here at the American Association for Pediatric Ophthalmology and Strabismus (AAPOS) 36th Annual Meeting.
"There have been no other long-term outcome studies of this form of esotropia in the literature," reported lead study author Sarah Jacobs, a 4-year medical student at Mayo Medical School in Rochester, Minnesota, during her presentation — which was named by the AAPOS as one of the top 10 "Best of Show" posters at the event.
"There have been short-term follow-up studies and smaller cohort studies, but this is the largest study of its type that has been done for this condition," added Ms. Jacobs.
Long-Term Results
The investigators evaluated the medical records of all pediatric patients between the ages of 6 months and 19 years who were diagnosed as having ANAET at the Mayo Clinic between January 1965 and December 1994 (n = 176, 61% male).
"This represented an incidence of 1 in 284 live births," said Ms. Jacobs.
"It was an interesting patient group that 10 or 15 years ago very few people really understood or knew much about," added principal investigator Brian G. Mohney, MD, professor of ophthalmology at the Mayo Clinic.
Diagnosis of ANAET was given at a median age of 4.3 years (range, 11 months to 18.2 years). Although 11% were diplopic at initial presentation, "none of the study patients were subsequently diagnosed with an intracranial malignancy," report the study authors.
A total of 73% of the patients (n = 129) underwent at least 1 strabismus surgery, 16.5% had a second surgery, and 2.8% had a third.
During a mean follow-up of 10.8 years (range, 0 days to 37 years), 70.3% of the postoperative patients had 10 or less prism diopters of deviation on final examination. In addition, 64% of all study patients regained some stereoacuity (median, 800 seconds of arc) and 7.4% regained normal stereopsis.
"Our study showed that 1 decade after a single surgery, two-thirds of these patients were within 10 prism diopters of orthotropia and 1 in 13 of all patients had normal stereopsis," said Ms. Jacobs. "So there were good outcomes, especially with surgical intervention."
"In summary, our findings show that ANAET is a lot more common than conventionally thought and that the incidence of intracranial lesion is a lot less common than typically thought," she added.
For clinicians who wonder whether they should perform magnetic resonance imaging (MRI) when a child comes in with an ANAET, "I'd say that, looking at our numbers, where none of the patients in our series had an intracranial lesion, it's really not cost-effective or clinically warranted to reflexively do an MRI in these kids unless there's a systemic neurologic abnormality present," said Ms. Jacobs.
"In this day and age where you're trying to wisely use healthcare dollars, you just don't need to scan every child who comes in with this condition unless there are other signs," reiterated Dr. Mohney.
Real Value From an Important Study
"I think this is an important study because it looked at kids with crossed eyes who don't have any obvious reason for having crossed eyes, which we call [ANAET]," said poster session comoderator Stephen Christiansen, MD, pediatric ophthalmologist and chair of the Ophthalmology Department at Boston University in Massachusetts and member of the AAPOS Program Committee.
"These are kids that we've always worried about because they don't need glasses and weren't born with esotropia. So why did they get it? The worry is that they have a central nervous system tumor," said Dr. Christiansen, who was not involved with this study.
"To have this cohort of patients, where a substantial number had diplopia (double vision), and be able to follow them for a very long period of time and find that they don't have tumors seems quite important."
He noted that he had some concerns with the investigators' inclusion and exclusion criteria, which may affect their data in the long term. "However, I still think that this is a substantial study and follows up well on some of the work that Dr. Mohney has done in the past. There's a lot of real value here and a lot that we'll learn from it."
"I'd say the key takeaway is that many of these children with [ANAET] ultimately are healthy children who can have very good outcomes," concluded Dr. Christiansen.
Ms. Jacobs, Dr. Mohney, and Dr. Christiansen disclosed no relevant financial relationships.
American Association for Pediatric Ophthalmology (AAPOS) 36th Annual Meeting: Abstract 74/Poster 10. Presented April 15, 2010.