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Effects of glucocorticoids on radiological progression in rheumatoid arthritis

  • Review
  • Intervention

Authors


Abstract

Background

Glucocorticoid use in rheumatoid arthritis (RA) is widespread. Two Cochrane Reviews have been published examining the short term clinical benefit of low dose glucocorticoids compared to non-steroidal anti-inflammatory drugs and demonstrate good short term and medium term clinical benefits. The possibility that glucocorticoids may have a fundamental 'disease modifying' effect in RA, which would be seen by a reduction in the rate of radiological progression, has been raised by several authors.

Objectives

To perform a systematic review of studies evaluating glucocorticoid efficacy in inhibiting the progression of radiological damage in rheumatoid arthritis.

Search methods

A search of MEDLINE (from 1966 to 22 February 2005) and the Cochrane Central Register of Controlled Trials was undertaken, using the terms 'corticosteroids' and 'rheumatoid arthritis' expanded according to the Cochrane Collaboration recommendations. Identified abstracts were reviewed and appropriate reports obtained in full. Additional reports were identified from the reference lists and from expert knowledge.

Selection criteria

Randomized controlled or cross-over trials in adults with a diagnosis of rheumatoid arthritis in which prednisone or a similar glucocorticoid preparation was compared to either placebo controls or active controls (i.e. comparative studies) and where there was evaluation of radiographs of hands, or hands and feet, or feet by any standardised technique. Eligible studies had at least one treatment arm with glucocorticoids and one without glucocorticoids.

Data collection and analysis

Standardised data extraction obtained the mean and standard deviation (SD) of change in erosion scores over 1 year or 2 years. (Where SD for change was not given a conservative estimate was taken from baseline data.) At least two authors selected the studies and extracted the data. Radiographic erosion scores were expressed as a percentage of the maximum possible score for the method used. The results were pooled after weighting in a random effects model to provide a standardised mean difference (SMD).

Main results

The initial search produced 217 citations, and 15 were added from experts, abstracts and review of reference lists. Authors of 4 trials being prepared for publication (and subsequently published) kindly shared their data. After application of eligibility criteria 15 studies and 1,414 patients were included. The majority of trials studied early RA (disease duration up to 2 years), and the mean cumulative dose of glucocorticoid was 2,300 mg prednisone equivalent (range 270 mg - 5,800 mg) over the first year. Glucocorticoids were mostly added to other disease modifying anti-rheumatoid drug (DMARD) treatment. The standardised mean difference in progression was 0.40 in favour of glucocorticoids (95% CI 0.27, 0.54). In studies lasting 2 years (806 patients included), the standardised mean difference in progression in favour of glucocorticoids at 1 year was 0.45 (0.24, 0.66) and at 2 years was 0.42 (0.30, 0.55). All studies except one showed a numerical treatment effect in favour of glucocorticoids. The beneficial effects of glucocorticoids were generally achieved when used in conjunction with other DMARD treatment.

Authors' conclusions

Even in the most conservative estimate, the evidence that glucocorticoids given in addition to standard therapy can substantially reduce the rate of erosion progression in rheumatoid arthritis is convincing. There remains concern about potential long-term adverse reactions to glucocorticoid therapy, such as increased cardiovascular risk, and this issue requires further research.

摘要

背景

類固醇用於治療類風濕性關節炎之X光進展效果

類固醇用於治療類風濕性關節炎是常見處置,兩篇Cochrane Reviews檢視比較低劑量類固醇與非類固醇消炎止痛藥短期效果,結果顯示良好的短期及中期效果。類固醇對於類風濕性關節炎的治療因有些作者發現有減緩影像學'的進展,而提出有疾病修飾的效果。

目標

研究整體回顧類固醇用於治療類風濕性關節炎對減緩X光進展的效果。

搜尋策略

搜尋包括MEDLINE (from 1966 to 22 February 2005) and the Cochrane Central Register of Controlled Trials。同時手動搜尋回顧文章之參考文獻及詢問專家。

選擇標準

隨機對照試驗或交叉試驗研究,成人類風濕性關節炎使用類固醇治療比上安慰劑、或一種其它治療的研究,評估減緩手腳關節X光進展的效果。選入研究為至少一組使用類固醇,另一組不使用類固醇。

資料收集與分析

收集1到2年後關節侵蝕分數(Erosion score)改變的平均數與標準差。至少兩位作者進行資料摘錄,並對每篇試驗研究的品質已經過效度評估之工具進行評估。關節侵蝕分數以最高可能分數的百分比表示。資料使用隨機效果模型統合分析,並以標準化平均差異(SMD)表示。

主要結論

最後15個研究,包含1414例病患於分析中。多數研究早年﹝疾病至多2年﹞類風濕性關節炎,類固醇第一年累積量2,30 g prednisone相當劑量 (rang 70 mg – 5,800 mg)。類固醇通常加上病程修飾藥物DMARD (disease modifying antirheumatoid drug)治療,類固醇對X光進展關節侵蝕標準化平均差異(SMD) 0.40 (95% CI 0.27, 0.54)。超過2年研究 (806位),SMD在1年為0.45 (0.24, 0.66),在2年為0.4 0.30, 0.55)。除一報告外皆顯示類固醇有效,類固醇通常加上病程修飾藥物一起使用。

作者結論

即使最保守估計,類固醇加上病程修飾藥物使用可大量減少類風濕性關節炎關節侵蝕的X光進展。因類固醇使用造成的長期副作用,如心血管疾病等,需進一步研究。

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

此Cochrane review摘要了我們所知道有關低劑量類固醇藥丸,如prednisone對類風濕關節炎病程進展的效果。文獻回顧顯示:在類風濕關節炎的患者,低劑量類固醇藥丸:可減少疾病在X光的進展多1至2年。這一結果是基於高品質的證據。這樣的好處發生在已經使用疾病修飾抗風濕藥物(DMARD)的患者,因此這樣做的好處是超越任何DMARDs所擁有的好處。這些結果在已經有類風濕關節炎少於 2年的患者身上是真的。很可能類固醇在患有風濕病 3至4年的病人會有相同的效果,但我們不知道是否有更長患病時間的人也可同理得證。長期的類固醇影響尚不清楚。什麼是類風濕關節炎與為何要使用類固醇?類風濕關節炎是一種疾病,指人體的免疫系統攻擊其自身的健康組織。攻擊大多發生在關節(尤其是在手和腳),造成關節紅腫,疼痛,腫脹和熱(發炎)。糖皮質激素也被稱為glucocorticosteroids,或有時只是稱'類固醇藥物,雖然有許多其他類型的類固醇。他們以藥片形式服用長達 7個月,並已被證實可以改善類風濕關節炎症狀。但是服用類固醇仍然有一些長期危害要注意,如心臟疾病。類風濕關節炎也分解和侵蝕受影響關節的軟骨和骨骼。這侵蝕不能被看見,需用X光測量。更多X光下侵蝕通常意味著該疾病的進展或惡化。是否糖皮質激素可以減緩侵蝕和疾病的進展有一些爭論。什麼是類固醇對類風濕關節炎進展的效果?這些研究看了類風濕患者長達 2年。低劑量的類固醇藥片,通常會與疾病修飾抗風濕藥物(DMARD)一起使用。類固醇減少疾病在X 光的進展多1至2年。這一結果是基於高品質的證據。害處沒有被發現。我們往往沒有確切有關副作用和併發症的資訊。尤其是罕見但嚴重的副作用與長期副作用。低劑量的類固醇可能不會帶來副作用,但可能出現的副作用包括骨質疏鬆症或心臟問題。

Plain language summary

Glucocorticoids for rheumatoid arthritis

This summary of a Cochrane review presents what we know from research about the effect of low dose glucocorticoid pills, such as prednisone, on the progress of rheumatoid arthritis. The review shows that:

In people with rheumatoid arthritis, low dose glucocorticoid pills:

- reduce the progression of the disease on x-rays over 1 to 2 years.

This result is based on high quality evidence.

This benefit occurred in people already taking a disease-modifying anti-rheumatoid drug (DMARD) and therefore this benefit is over and above any benefits from the DMARDs.

These results were true in people that had rheumatoid arthritis for less than 2 years. It seems likely that glucocorticoids would have the same effect in people who have had rheumatoid for 3 to 4 years, but it is not known whether this is true in people who have had it for longer.

The long term effects of glucocorticoids are not known.

What is rheumatoid arthritis and why use glucocorticoids?
Rheumatoid arthritis is a disease in which the body's immune system attacks its own healthy tissues. The attack happens mostly in the joints (especially in the hands and feet) and causes redness, pain, swelling and heat in the joint (inflammation). Glucocorticoids are also known as glucocorticosteroids, or sometimes just 'steroids', although there are many other types of steroids. They are taken as pills for up to 7 months and have already been shown to improve the symptoms of rheumatoid arthritis. There is however still some concern about the long term harms, such as heart problems, when taking glucocorticoids.

Rheumatoid arthritis also breaks down and erodes away the cartilage and bones in the affected joints. This erosion cannot be seen and is measured by x-rays. More erosion on an x-ray usually means that the disease is progressing or worsening. There is some debate about whether glucocorticoids can slow the erosion and the progression of the disease.

What are the effects of glucocorticoids on the progress of rheumatoid arthritis?
The studies looked at people who had rheumatoid for up to 2 years. Low doses of glucocorticoid pills were taken and usually with a disease-modifying anti-rheumatoid drug (DMARD).

Glucocorticoids reduce progression of the disease on x-rays over 1 to 2 years. This result is based on high quality evidence.

Harms were not reviewed. We often do not have precise information about side effects and complications. This is particularly true for rare but serious side effects and long term side effects. Low doses of glucocorticoids may not lead to side effects, but possible side effects may include osteoporosis or heart problems.

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