Rofecoxib for osteoarthritis

  • Review
  • Intervention

Authors


Abstract

Background

Editor's note: The anti-inflammatory drug rofecoxib (Vioxx) was withdrawn from the market at the end of September 2004 after it was shown that long-term use (greater than 18 months) could increase the risk of heart attack and stroke. Further information is available at www.vioxx.com.

Osteoarthritis is a chronic disease of the joints, characterised by joint pain, stiffness and loss of physical function. Its onset is age-related and occurs usually between the ages of 50 and 60. It is the commonest cause of disability in those aged over 65, with OA of the knee and/or hip affecting over 20 per cent of the elderly population.

Objectives

To establish the efficacy and safety of rofecoxib in the management of OA by systematic review of available evidence.

Search methods

We searched the following databases up to August 2004: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Research Register, NHS Economic Evaluation Database, Health Technology Assessment Database. The bibliographies of retrieved papers and content experts were consulted for additional references.

Selection criteria

All eligible randomised controlled trials (RCTs) were included. No unpublished RCTs were included in this edition of the review.

Data collection and analysis

Data were abstracted independently by two reviewers. A validated checklist was used to score the quality of the RCTs. Comparable trials were pooled using fixed effects model.

Main results

Twenty-six RCTs were included. The comparators were placebo, diclofenac, ibuprofen, naproxen, nimesulide, nabumetone, paracetamol, celecoxib and Arthrotec. The evidence reviewed indicated that rofecoxib was more effective than placebo (patient global response RR 1.75 95% CI: 1.35, 2.26) but was associated with more adverse events (RR 1.32 95% CI 1.11, 1.56). There were no consistent differences in efficacy between rofecoxib and any of the active comparators at equivalent doses. Endoscopic studies indicated that compared to ibuprofen 800mg three times a day, rofecoxib caused fewer erosions and gastric ulcers at doses of 25mg and 50mg; the difference in duodenal ulcers was evident only at a dose of 25mg. Rofecoxib 50mg also caused more endoscopically observed ulcers greater than rofecoxib 25mg (RR 2.48 CI: 1.21, 5.11). Very few of the trials reported overall rates of GI adverse events although rofecoxib was found to cause fewer GI events than naproxen. Only one of the nine trials comparing rofecoxib to celecoxib reported on the overall rates of GI events and this was a comparison of the higher recommended dose of rofecoxib with the lower recommended dose of celecoxib. Similarly, the three trials in older hypertensive patients that examined the cardiovascular safety of rofecoxib and celecoxib used non-comparable doses; the results of these studies indicated that rofecoxib caused more patients to have oedema and a clinically significant increase in systolic blood pressure. This difference between rofecoxib and celecoxib was not evident in studies conducted in more general populations.

Authors' conclusions

Rofecoxib was voluntarily withdrawn from global markets in October 2004 therefore there are no implications for practice concerning its use. There remains a number of questions over both the benefits and risks associated with Cox II selective agents and further work is ongoing.

摘要

背景

Rofecoxib治療退化性關節炎

研究顯示Vioxx使用超過18個月後有增加心血管疾病及中風危險,故於2004年9月底退出市場。退化性關節炎是慢性關節疾病引起關節疼痛、僵硬及喪失功能。通常始發生於50 – 60歲老人,並為65歲以上老人行動不良最常見原因之一。膝及髖退化性關節炎影響超過20% 老人。

目標

評估rofecoxib治療退化性關節炎之效果及安全性。

搜尋策略

搜尋到2004年8月,包括MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Research Register, NHS Economic Evaluation Database, Health Technology Assessment Database。同時手動搜尋所選文章之參考文獻及詢問專家。

選擇標準

採用所有隨機對照試驗。

資料收集與分析

兩位作者獨立進行資料摘錄,並對試驗研究的品質進行評估。使用固定效應模型(fixedeffects model)分析。

主要結論

26個研究包含於分析中。比較組為安慰劑, diclofenac, ibuprofen, naproxen, nimesulide, nabumetone, paracetamol, celecoxib and Arthrotec。 26個研究包含於分析中。比較組為安慰劑, diclofenac, ibuprofen, naproxen, nimesulide, nabumetone, paracetamol, celecoxib and Arthrotec。 Rofecoxib比安慰劑有效(病人整體反應 R 1.75 95% CI: 1.35, 2.26)但副作用較多(RR 1.32 95% CI 1.11, 1.56)。Rofecoxib與其他消炎止痛藥無顯著差異。胃鏡顯示Rofecoxi 5mg及50mg比ibuprofen 800mg一日3次較少胃糜爛與胃潰瘍,12指腸潰瘍僅在25mg Rofecoxib組較少。50mg比25mg rofecoxib引起較多潰瘍(RR 2.48 CI: 1.21, 5.11)。雖然rofecoxib比naproxen少造成潰瘍,很少試驗報告整體胃腸副作用。只有9篇中1篇比較rofecoxib與celecoxib整體胃腸副作用,但為高劑量rofecoxib比上低劑量celecoxib。同樣的比較也發生於rofecoxib與celecoxib於高血壓患者之心臟病,也有高低不同劑量的比較問題。研究顯示rofecoxib造成較多水腫與收縮壓上昇。rofecoxib與celecoxib在一般群眾差異不顯著。

作者結論

2004年10月rofecoxib (Vioxx)自動退出市場。COX2抑制劑之效果及安全性有待進一步評估。

翻譯人

本摘要由林口長庚醫院余光輝翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

編者按:抗炎藥rofecoxib(Vioxx)是在2004年9月底從市場上撤回,因為被發現長期使用(大於 18個月)可能會增加心臟病發作和中風的風險。更多信息可在www.vioxx.com。是否rofecoxib可治療退化性關節炎和其安全性如何呢?要回答這個問題,科學家們發現和分析26個研究。這些研究納入超過20 000個退化性關節炎患者,並且追蹤持續1年。研究比較服用rofecoxib 12.5,25或50毫克,每天一次與服用安慰劑(糖丸)或其他NSAIDs,如diclofenac, ibuprofen, naproxen, nimesulide, nabumetone, paracetamol (Tylenol), celecoxib 或 Arthrotec。這些研究提供了今日我們所擁有最好的證據。什麼是退化性關節炎和rofecoxib如何能幫助患者?退化性關節炎(OA)是關節炎最常見的形式,會影響手,髖部,肩膀和膝蓋。在OA軟骨,保護兩端骨頭免於骨破裂,導致疼痛和腫脹。rofecoxib通常稱為 ‘COX II抑製劑’ ,是一種新的非類固醇抗炎藥(NSAIDs)用以減輕疼痛和炎症。其他NSAIDs,如naproxen (Naprosyn)也用於類似病症,但被提出警告,可能會引起下列嚴重副作用,如消化道潰瘍,出血和穿孔。Rofecoxib被認為在腸胃道作用比其他NSAIDs安全。Rofecoxib在2004年10月被退出市場。一項研究顯示,比起服用糖丸,服用Rofecoxib來預防罹患結腸癌的病患有更多的心臟病發作和中風。Rofecoxib應用於OA的試驗顯示怎樣的結果?研究表明,比起服用糖丸,服用Rofecoxib的患者改善較多。 項研究表明, ‧服用糖丸100位中的29個患者整體感覺較好 ‧每天服用rofecoxib 12.5mg100位中的53個患者整體感覺較好。研究還表明,使用rofecoxib或不同的NSAID其改善是大致相同的。在研究中他的安全性如何?很少的研究記錄和報告了胃部的問題。比起使用糖丸,使用rofecoxib的患者有較多的腎病,水滯留和高血壓,但有胃問題的病患數是大致相同。與其他NSAIDs相比,比起服用ibuprofen(800毫克,每日3次)或naproxen,少數人服用25或50毫克rofecoxib有胃的問題。Rofecoxib引起的腹瀉也比arthrotec少。什麼是底線?Rofecoxib在2004年10月正式退出了世界各地市場,已不再被使用。在考慮哪些非類固醇抗炎藥(NSAID)可被使用,必須記住藥物的效果和安全,人與人之間和藥物間都是不同的。其效果和安全性還取決於劑量,以及如何在體內發生作用。對於其他的COX  2抑製劑而言,仍然有其效果和安全性的疑問,更多的研究正在進行中。

Plain language summary

Rofecoxib for osteoarthritis

Editor's note: The anti-inflammatory drug rofecoxib (Vioxx) was withdrawn from the market at the end of September 2004 after it was shown that long-term use (greater than 18 months) could increase the risk of heart attack and stroke. Further information is available at www.vioxx.com.

Does Rofecoxib work for treating osteoarthritis and how safe is it?
To answer this question, scientists found and analyzed 26 studies. These studies included over 20 000 people with osteoarthritis and lasted up to 1 year. Studies compared people taking rofecoxib at 12.5, 25 or 50 mg once a day to people taking a placebo (sugar pill) or other NSAIDs such as diclofenac, ibuprofen, naproxen, nimesulide, nabumetone, paracetamol (Tylenol), celecoxib or Arthrotec. These studies provide the best evidence we have today.

What is osteoarthritis and how could rofecoxib help?
Osteoarthritis (OA) is the most common form of arthritis that can affect the hands, hips, shoulders and knees. In OA, the cartilage that protects the ends of the bones breaks down and causes pain and swelling. Rofecoxib is often referred to as a 'COX II inhibitor' and is one of the new non-steroidal anti-inflammatory drugs (NSAIDs) prescribed to decrease pain and inflammation. Other NSAIDS, such as naproxen (Naprosyn) are also prescribed but they come with warnings that they may cause stomach problems such as ulcers, bleeds and sores that can be serious. Rofecoxib is thought to be safer on the stomach than other NSAIDS.

Rofecoxib was taken off the market in October 2004. A study had shown that people taking rofecoxib to prevent colon cancer had more heart attacks and strokes than people taking a sugar pill.

What did studies testing rofecoxib in OA show?
Studies showed people taking rofecoxib improved more than people taking a sugar pill.

Three studies showed that
• 29 out of 100 people felt better overall with a sugar pill
• 53 out of 100 people felt better overall with rofecoxib at 12.5 mg per day.

Studies also showed that improvements were about the same whether people took rofecoxib or a different NSAID.

How safe was it in the studies?
Very few studies recorded and reported stomach problems. When rofecoxib was compared to a sugar pill, more people taking rofecoxib had kidney problems, water retention and high blood pressure but the number of people with stomach problems was about the same.

When compared to other NSAIDs, less people taking 25 or 50 mg rofecoxib had stomach problems than when taking ibuprofen (800 mg three times a day) or naproxen. Rofecoxib also caused less diarrhea than arthrotec.

What is the bottom line?
Rofecoxib was withdrawn from the world wide market in October 2004 and is no longer available.

When considering which non-steroidal anti-inflammatory drug (NSAID) to use, it must be remembered that the effects and safety of a drug is different among people and depends on the drug. The effect and safety also depends on the dose and how it acts in the body.

There are still questions about the effects and safety of other Cox-II inhibitors and more research is being done.

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