June 18, 2007（巴塞隆納訊）－根據一研究團隊於歐洲風濕學學會發表的研究結果，罹患僵直性脊椎炎（AS）病患接受infliximab（Remicade，Centocor藥廠製造）治療的好處可以持續到停藥兩年後。
主要研究者德國柏林大學風濕學教授Jurgen Braun醫師在他的發表會中表示，治療對脊椎發炎也有幫助，這是僵直性脊椎炎一種常見且使人衰弱的病徵。
Braun醫師與其共同研究者想要知道infliximab對於脊椎活動度的好處在長期治療後是否可以持續下去，因此，他們延長ASSERT（ the Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy）研究，這是一項針對發病中AS病患進行的第三期、隨機分派、安慰劑控制、多中心試驗。
在原來的研究中，研究者隨機分派病患接受持續輸注安慰劑或是infliximab（5 mg/kg）在第0、與6週且之後每6週投予一次；在第24週時，78位接受安慰劑轉而接受治療，這些病患治療到第96週；在第36週維持到第96週，201位病患原本被隨機分派接受infiximab，如果貝氏僵直性脊椎炎活性指數連續兩次測量都高於3分，則增加劑量至7.5 mg/kg；研究者於第102週時，也就是試驗結束時評估所有病患。
在之後的後續追蹤，研究者也紀錄病患的貝氏僵直性脊椎炎度量指標（BASMI，自0到10分），且令病患深呼吸以評估活動範圍；他們定義臨床上有意義的改善為BASMI指標至少上升1分；接著研究者比較治療組之間的療效差異。
在第24週時，接受活性治療的病患，其BASMI分數平均降低0.2分，相較於安慰劑組則是平均下降0.7分（P=0.02）﹔治療組的胸部擴張程度增加43.6%，相較於安慰劑組則僅18.7%（P=0.03）；在那時候，研究者紀錄治療組中有51%病患有臨床上顯著改善，相較於安慰劑組僅有31%（P<0.01）；那些在治療組的病患，在第24週後，BASMI分數與胸部擴張程度仍然持續改善，在第102週時持續增加；在第24週轉為infliximab之後，那些原本使用安慰劑的病患，BASMI分數與胸部擴張程度與那些持續治療的病患，研究者在第54、78與102週時評估的反應相似。
EULAR科學委員會主席、同時也是蘇格蘭格拉斯哥大學風濕學教授Iain McInnes醫師在一項訪談中表示，ASSERT研究是一項對於infliximab可能對僵直性脊椎炎提供怎樣好處的有趣研究；McInnes醫師並未參與這項研究。
他表示，研究顯示，在臨床症狀上有顯著改善，且這對病患來說是最重要的事情，因為我們目前對於僵直性脊椎炎的治療仍然有限；脊椎MRI（核磁共振造影）上的改善代表治療是針對核心發炎事件，但在此時，有點令人失望，我們以放射線結構疾病分析上並未看到改善；儘管如此，顯然的，這是個令人興奮的開始，且我們有更多的研究需要進行。
該試驗由Centocor藥廠贊助，該公司為Remicade製造廠商。Braun醫師與Mclnnes醫師表示並無相關資金上的往來。
Infliximab Benefits Continue for 2 Years in Patients with Ankylosing Spondylitis
By Paula Moyer, MA
Medscape Medical News
June 18, 2007 (Barcelona) — Patients with ankylosing spondylitis (AS) continue to benefit from treatment with infliximab (Remicade, Centocor Pharmaceuticals) after 2 years of treatment, according to a team of investigators who presented their findings here at the annual meeting of the European Congress of Rheumatology.
"Our findings show that treatment with infliximab improves spinal mobility and that this improvement can be maintained when it is combined with physiotherapy," said principal investigator Jurgen Braun, MD, professor of rheumatology at the Free University of Berlin, in Germany, in his presentation. "Treatment also benefited spinal inflammation, a common and debilitating manifestation of ankylosing spondylitis."
Dr. Braun and his coinvestigators wanted to know if the spinal mobility benefits associated with infliximab persisted after long-term treatment. Therefore, they conducted an extension phase of the Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT), a phase 3, randomized, double-blind, placebo-controlled, multicenter trial of patients with active AS.
In the original study, the investigators randomized patients to receive infusions of either placebo or infliximab (5 mg/kg) at weeks 0, 2, and 6, and every 6 weeks thereafter. At week 24, the 78 patients on placebo crossed over to treatment, which they continued through week 96. Starting at week 36, and continuing through week 96, the 201 patients originally randomized to infliximab increased their dose to 7.5 mg/kg if they had a Bath Ankylosing Spondylitis Disease Activity Index of more than 3 on 2 consecutive visits. The investigators assessed all of the patients at week 102, at the end of the study.
At follow-up appointments, the investigators also documented patients' Bath Ankylosing Spondylitis Metrology Index (BASMI, ranging from 0 to 10) and their chest expansion to assess range of motion. They defined clinically meaningful improvement as a change of at least 1 in the BASMI score. They then compared the difference in changes between treatment groups.
At week 24, patients on active treatment had an average decrease in BASMI score of 0.2, compared with an average decrease of 0.7 in the placebo group (P = .02). Chest expansion increased an average of 43.6% in the treatment group and 18.7% in the placebo group (P = .03). At that time, the investigators documented a clinically meaningful improvement in BASMI score in 51% of those in the treatment group and in 31% in the placebo group (P < .01). Those in the treatment group also had gradual improvement in BASMI scores and chest expansion after week 24, which they sustained at week 102. After switching to infliximab at week 24, those originally on placebo had improvements in BASMI scores and chest expansion similar to those in the group on continuous treatment when the investigators evaluated them at weeks 54, 78, and 102.
"The ASSERT study is a very interesting examination of what infliximab might offer patients with ankylosing spondylitis," said Iain McInnes, MD, chairman of the EULAR Scientific Committee and professor of rheumatology at the University of Glasgow, in Scotland, in an interview. Dr. McInnes was not involved in the study.
"There are clear improvements in clinical symptoms, and that is a major issue for patients, since our therapeutic options are limited in ankylosing spondylitis at the moment," he said. "MRI [magnetic resonance imaging] improvements in the spine suggest this treatment is getting at core inflammatory events. It's a little disappointing that, at the moment, we are not seeing changes in the radiographic structural features of the disease. But, clearly, it is an exciting start and we have more work to do."
The study was funded by Centocor, Inc., which manufactures Remicade. Neither Dr. Braun nor Dr. McInnes reported any relevant financial relationships.
EULAR 2007: Abstract FRI0368. Presented June 15, 2007.
作者：
Paula Moyer, MA 2007-7-10