Viscosupplementation for the treatment of osteoarthritis of the knee

 

Abstract

Background

Osteoarthritis (OA) is the most prevalent chronic joint disorder worldwide and is associated with significant pain and disability.

Objectives

To assess the effects of viscosupplementation in the treatment of OA of the knee. The products were hyaluronan and hylan derivatives (Adant, Arthrum H, Artz (Artzal, Supartz), BioHy (Arthrease, Euflexxa, Nuflexxa), Durolane, Fermathron, Go-On, Hyalgan, Hylan G-F 20 (Synvisc Hylan G-F 20), Hyruan, NRD-101 (Suvenyl), Orthovisc, Ostenil, Replasyn, SLM-10, Suplasyn, Synject and Zeel compositum).

Search methods

MEDLINE (up to January (week 1) 2006 for update), EMBASE, PREMEDLINE, Current Contents up to July 2003, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched. Specialised journals and reference lists of identified randomised controlled trials (RCTs) and pertinent review articles up to December 2005 were handsearched.

Selection criteria

RCTs of viscosupplementation for the treatment of people with a diagnosis of OA of the knee were eligible. Single and double-blinded studies, placebo-based and comparative studies were eligible. At least one of the four OMERACT III core set outcome measures had to be reported (Bellamy 1997).

Data collection and analysis

Each trial was assessed independently by two reviewers for its methodological quality using a validated tool. All data were extracted by one reviewer and verified by a second reviewer . Continuous outcome measures were analysed as weighted mean differences (WMD) with 95% confidence intervals (CI). However, where different scales were used to measure the same outcome, standardized mean differences (SMD) were used. Dichotomous outcomes were analyzed by relative risk (RR).

Main results

Seventy-six trials with a median quality score of 3 (range 1 to 5) were identified. Follow-up periods varied between day of last injection and eighteen months. Forty trials included comparisons of hyaluronan/hylan and placebo (saline or arthrocentesis), ten trials included comparisons of intra-articular (IA) corticosteroids, six trials included comparisons of nonsteroidal anti-inflammatory drugs (NSAIDs), three trials included comparisons of physical therapy, two trials included comparisons of exercise, two trials included comparisons of arthroscopy, two trials included comparisons of conventional treatment, and fifteen trials included comparisons of other hyaluronans/hylan. The pooled analyses of the effects of viscosupplements against 'placebo' controls generally supported the efficacy of this class of intervention. In these same analyses, differential efficacy effects were observed for different products on different variables and at different timepoints. Of note is the 5 to 13 week post injection period which showed a percent improvement from baseline of 28 to 54% for pain and 9 to 32% for function. In general, comparable efficacy was noted against NSAIDs and longer-term benefits were noted in comparisons against IA corticosteroids. In general, few adverse events were reported in the hyaluronan/hylan trials included in these analyses.

Authors' conclusions

Based on the aforementioned analyses, viscosupplementation is an effective treatment for OA of the knee with beneficial effects: on pain, function and patient global assessment; and at different post injection periods but especially at the 5 to 13 week post injection period. It is of note that the magnitude of the clinical effect, as expressed by the WMD and standardised mean difference (SMD) from the RevMan 4.2 output, is different for different products, comparisons, timepoints, variables and trial designs. However, there are few randomised head-to-head comparisons of different viscosupplements and readers should be cautious, therefore, in drawing conclusions regarding the relative value of different products. The clinical effect for some products, against placebo, on some variables at some timepoints is in the moderate to large effect-size range. Readers should refer to relevant tables to review specific detail given the heterogeneity in effects across the product class and some discrepancies observed between the RevMan 4.2 analyses and the original publications. Overall, the analyses performed are positive for the HA class and particularly positive for some products with respect to certain variables and timepoints, such as pain on weight bearing at 5 to 13 weeks postinjection.

In general, sample-size restrictions preclude any definitive comment on the safety of the HA class of products; however, within the constraints of the trial designs employed no major safety issues were detected. In some analyses viscosupplements were comparable in efficacy to systemic forms of active intervention, with more local reactions but fewer systemic adverse events.

In other analyses HA products had more prolonged effects than IA corticosteroids. Overall, the aforementioned analyses support the use of the HA class of products in the treatment of knee OA.

 

Plain language summary

Viscosupplementation for the treatment of osteoarthritis of the knee

Osteoarthritis (OA) is the most common form of chronic arthritis worldwide. Hyaluronan and hylan (HA) products provide opportunity to treat OA in individual knee joints. To evaluate the efficacy, effectiveness and safety of HA products, in knee OA, we have conducted a systematic review using Cochrane methodology. The analyses support the contention that the HA class of products is superior to placebo. There is considerable between-product, between-variable and time-dependent variability in the clinical response. The clinical effect for some products against placebo on some variables at some time points is in the moderate to large effect size range. In general, sample size restrictions preclude any definitive comment on the safety of the HA class of products, however, within the constraints of the trial designs employed, no major safety issues were detected. The analyses suggest that viscosupplements are comparable in efficacy to systemic forms of active intervention, with more local reactions but fewer systemic adverse events, and that HA products have more prolonged effects than IA corticosteroids. Overall, the aforementioned analyses support the use of the HA class of products in the treatment of knee OA.

 

摘要

背景

黏液補充治療膝退化性關節炎

膝退化性關節炎是常見慢性關節疾病且與疼痛與行動障礙有關。

目標

研究關節內注射玻尿酸黏液補充治療膝退化性關節炎的效果。產品為hyaluronan and hylan 衍生物(Adant, Arthrum H, Artz (Artzal, Supartz), BioHy (Arthrease, Euflexxa, Nuflexxa), Durolane, Fermathron, GoOn, Hyalgan, Hylan GF 20 (Synvisc Hylan GF 20), Hyruan, NRD101 (Suvenyl), Orthovisc, Ostenil, Replasyn, SLM10, Suplasyn, Synject and Zeel compositum)。

搜尋策略

搜尋包括MEDLINE (up to January (week 1) 2006 for update), EMBASE, PREMEDLINE, Current Contents up to July 2003, and the Cochrane Central Register of Controlled Trials (CENTRAL)。同時手動搜尋RCT參考文獻到2005年12月。

選擇標準

隨機單盲或雙盲對照試驗研究黏液補充治療膝退化性關節炎的效果。至少報告四個OMERACT III核心指標中的一個才選入。

資料收集與分析

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。連續性資料使用加權平均差異分析，但用不同度量單位測同一指標時以標準平均差異分析，二分法類別資料使用相對風險(RR)來表示。

主要結論

76個研究平均品質指標3﹝範圍1到5﹞包含於分析中。各研究之追蹤時間由數天到１８個月不等。4個研究比較hyaluronan/hylan 與安慰劑(生理食鹽水注射或關節液抽取)，4個研究比較關節內注射類固醇，4個研究比較非類固醇消炎止痛藥，３個研究比較物理治療，２個研究比較運動，２個研究比較關節鏡，２個研究比較傳統治療，１５個研究比較其它hyaluronans/hylan。統合各黏液補充治療與安慰劑比較，一般支持黏液補充治療。不同產品在不同時間、不同指標，有不同的效果。注射５到１３週後疼痛改善28 to 54%及功能改善9 to 32%。整體而言，與非類固醇消炎止痛藥比效果相當，長期效益與關節內注射類固醇效果相當。整體而言，試驗中hyaluronan/hylan注射副作用較少。

作者結論

研究顯示黏液補充治療對疼痛與功能改善及病患整體評估有助益，尤其注射５到１３週後改善較多。但不同產品在不同時間、不同指標，有不同的效果，且僅有少數藥物間有直接比較，因此不同產品的相對價值下結論應小心。某些產品在不同時間、某些指標效果為中到大的效果。因各產品異質性及原論文與RevMan 4.2結果稍有不同關係，讀者應參考相關表格。整體而言，HA類黏液補充治療對疼痛與功能改善有助益，尤其在某些時間點與指標，例如５到１３週時負重改善。因樣本數限制安全性結論，但在研究中無重大副作用出現。某些分析顯示示黏液補充治療與某些全身性治療療效相當，但較多局部副作用與較少全身性副作用。某些分析顯示示黏液補充治療比關節內注射類固醇效果長。整體而言，支持黏液補充治療膝退化性關節炎。

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

膝退化性關節炎是常見慢性關節疾病。黏液補充治療Hyaluronan and hylan (HA)提供治療膝退化性關節炎的機會。整體而言，支持黏液補充類治療膝退化性關節炎比安慰劑好。但不同產品在不同時間、不同指標，有不同的效果，某些產品指標效果為中到大的效果。因樣本數少，限制安全性結論，但在研究中無重大副作用出現。某些分析顯示示黏液補充治療與某些全身性治療療效相當，但較多局部副作用與較少全身性副作用。黏液補充治療比關節內注射類固醇效果長。整體而言，支持黏液補充治療膝退化性關節炎。