リウマチ

FDA Turns Down Merck Arthritis Drug
By THE ASSOCIATED PRESS
Published: April 28, 2007

The Food and Drug Administration has rejected Merck & Company’s bid to win approval for a successor to Vioxx（ロフェコキシブ）, the arthritis medication that Merck withdrew from the market more than two years ago, the company said yesterday.

The decision had been widely expected ever since a panel of F.D.A. advisers （FDA諮問委員会）　voted two weeks ago by 20 to 1 against approval of the drug, Arcoxia（etoricoxib、エトリコキシブ、MK-0663、5-chloro-2-(6-methylpyridin-3-yl)-3-(4-methylsulfonylphenyl) pyridine）, because of concerns that it could cause as many as 30,000 heart attacks a year if widely used.

Like Vioxx, whose name has become almost synonymous with drug safety problems, Arcoxia is among a class of anti-inflammatory drugs called cox-2 inhibitors. Such medications were developed in the hope that they would be less likely to cause stomach bleeding than ibuprofen and naproxen＊.

But while they did prove to safeguard the stomach, they have been linked to heart risks. Merck withdrew Vioxx in September 2004 after research showed that it doubled the risk of heart attacks and strokes.

Despite the safety concerns in the United States, Arcoxia is on sale in 63 other countries. It brought in revenue of $265 million last year.

＊MEDAL（Multinational Etoricoxib and Diclofenac Athritis Long-term）スタディは、46カ国の1380施設で行われた3件の臨床試験（EDGE、EDGE II、MEDAL）の総称で、変形性関節炎（OA）または関節リウマチ（RA）約3万5000人を対象に、COX-2阻害薬エトリコキシブと、非選択的NSAIDsジクロフェナクの、心血管イベント発生率を比較している。
EDGE trialの結果はJ Rheumatol. 2007 Feb;34(2):408-20）に報告されていて、7111例のOAを対象にetoricoxib 90 mg qd (n = 3593) またはdiclofenac sodium（ボルタレン） 50 mg tid (n = 3518)に割付け、約9ヶ月間フォロー。その結果、消化器症状は有意にエトリコキシブが優っていた。また、血栓リスクも両者で同様であった[1.25 vs 1.15 events per 100 PY]. しかし、高血圧関連の有害事象はエトリコキシブ群で多かった(2.3% vs 0.7%; p < 0.001)。
　MEDAL試験(約35,000例の関節炎患者（OA7割、RA3割）を対象にした)では、エトリコキシブ（Arcoxia、メルク、米国未発売）は従来のNSAIDと比べた場合、心血管イベントに問題はないと報告されていたが（Lancet;368:1771,2006）、結局米国では上市に至らなかった。