【Cochrane简语概要】秋水仙碱对COVID-19感染者有效吗？

关键信息

○对于中度至重度COVID-19感染住院患者，秋水仙碱可能几乎没有获益；我们不确定它的副作用如何。

○对于没有症状或轻度COVID-19感染的非住院患者，我们不确定秋水仙碱是否可以防止死亡或副作用，但它可能会稍微减少患者住院治疗的需要、减少死亡以及严重的副作用。

○ 将来的研究应评估无症状患者或轻度COVID-19感染患者以及非严重副作用患者的生活质量，并将秋水仙碱与其他治疗COVID-19的药物（如皮质类固醇）进行比较。

（图片来源于zhiku.bopuyun.com）

什么是秋水仙碱？

秋水仙碱是一种用于减轻肿胀和炎症的药物，因此它可以减轻疼痛。它通常用于治疗痛风，痛风是一种使人的关节肿胀和疼痛的疾病。另一方面，秋水仙碱可能对某些患有健康问题的人有害，例如肾脏或肝脏问题，或者服用过多该物也会造成损伤。

秋水仙碱如何治疗COVID-19？

由于秋水仙碱是一种抗炎药；研究人员对它是否有助于减轻由 COVID-19引起的炎症感兴趣。

我们想探索什么？

我们想知道与安慰剂（一种外观和味道与秋水仙碱相同但不含活性成分的治疗剂）或单独的常规护理相比，秋水仙碱是否对COVID-19感染患者的治疗有效。我们以在医院接受治疗的中度或重度感染患者以及在社区接受治疗的轻度感染患者为对象进行了研究。我们对秋水仙碱对以下方面的影响非常感兴趣：

○ 死亡人数；

○ 人们的病情是否恶化或好转；

○ 生活质量

○ 严重或非严重性副作用

我们做了什么？

我们检索了将秋水仙碱伴随常规护理和常规护理（加/减安慰剂）进行比较的研究。研究可在世界任何地方进行，包括轻度感染、无症状、中度或重度COVID-19感染的人，无论其年龄、性别或者种族。

我们对比并总结了各项研究结果，基于研究方法和规模等因素来评定证据的质量等级。

我们发现了什么?

我们纳入了四项符合条件的随机对照试验。共3项试验涉及11525名住院患者，1项试验涉及4488名非住院患者。住院患者的平均年龄为64岁，非住院患者的平均年龄为55岁。两项研究将秋水仙碱和常规护理治疗与单独常规护理治疗进行了比较，还有两项研究将秋水仙碱与常规护理伴随安慰剂治疗进行了比较。没有研究报告有关患者生活质量的数据。我们还发现了17项正在进行的研究和11项已完成但未发表的研究。

主要研究结果

中度至重度COVID-19感染住院患者（三项研究，共计11525人）

○秋水仙碱可能不会使在接受治疗后28天内死亡的患者人数有所降低（两项研究，共计11445人）。

○秋水仙碱可能无法阻止患者病情恶化（两项研究，共计10916人），也可能不会改善患者病情（1项研究，共计11340人）。

○我们非常不确定秋水仙碱对疾病副作用和严重副作用的影响（两项研究，共计177人）。

无症状或轻度COVID-19感染的非住院患者（一项研究，共计4488人）

○我们不确定秋水仙碱是否能阻止患者在接受治疗28天后死亡。

○秋水仙碱可能会使患者住院或死亡的风险稍有降低。

○我们不确定秋水仙碱对疾病副作用的影响，但它可能会轻微减少严重副作用的发生。

证据的局限性是什么？

我们对证据质量的确定性受限。两项研究都没有使用安慰剂，所以每个人都知道哪位患者接受了秋水仙碱治疗，这可能会对结果造成影响。对于非住院患者来说，由于住院治疗和患者死亡的相关事件太少，所以无法确定证据质量。研究使用不同的方法来评估和报告不良影响，因此我们无法将研究综合为一个结果来做出判断。

证据的时效性如何？

证据更新至2021年5月21日。

编者按：这是一项实时系统综述。我们每周都会检索新的证据并在发现相关的新证据时更新本综述。欲了解本综述目前的情况，请参阅Cochrane系统综述数据库（the Cochrane Database of Systematic Reviews）。

作者结论: 

根据目前的证据，在因中度至重度COVID-19感染而住院的患者中，与单独使用安慰剂或实施标准治疗相比，秋水仙碱的使用可能对患者死亡率或临床进展几乎没有影响。我们不知道秋水仙碱是否会增加发生（严重）不良事件的风险。

我们不确定秋水仙碱对无症状感染者或轻度感染患者全因死亡率影响的证据。然而，与安慰剂相比，秋水仙碱可能会使28天内的住院人数或死亡人数略有减少，严重不良事件的发生率也有所降低。

没有任何一项研究报告了有关生活质量的数据，也没有比较秋水仙碱与其他药物或使用不同剂量秋水仙碱的益处和危害有何不同。

我们检索到17项正在进行的和11项已完成但尚未发表的RCT，我们希望在其结果可用时能够将其纳入本综述的未来版本。

编者按：由于本系统综述采用实时的方法，我们每周都会监测秋水仙碱随机对照试验最新公布的结果，并在其证据或我们对证据的确定性发生变化时更新综述。

作者:Mikolajewska A, Fischer A-L, Piechotta V, Mueller A, Metzendorf M-I, Becker M, Dorando E, Pacheco RL, Martimbianco ALC, Riera R, Skoetz N, Stegemann M；译者：牛秀岚，北京中医药大学人文学院2018级英语中医药国际传播方向；审校：李迅，北京中医药大学循证医学中心；编辑排版：索于思，北京中医药大学循证医学中心

相关文章链接

【Cochrane Plain Language Summary】

Is colchicine an effective treatment for people with COVID-19?

Key messages

○ In hospitalised people with moderate to severe COVID-19, colchicine probably has little to no benefit; we are uncertain about its side effects. 

○In non-hospitalised people with no symptoms or mild COVID-19, we are uncertain whether colchicine prevents deaths or side effects, however it probably reduces the need for hospitalisation or death and serious side effects slightly. 

○ Future studies should assess quality of life in people with no symptoms or mild COVID-19 and non-serious side effects and compare colchicine to other medicines for COVID-19, such as corticosteroids.

What is colchicine?

Colchicine is a medicine used to reduce swelling and inflammation and may consequently relieve pain. It is often used to treat gout, a condition where people’s joints become swollen and painful. On the other hand, colchicine can be harmful to people with some health conditions, such as kidney or liver problems, or if you take too much of it. 

How might colchicine treat COVID-19?

Since colchicine is an anti-inflammatory drug; researchers are interested in whether it might help with reducing inflammation caused by COVID-19. 

 What did we want to find out?

We wanted to know whether colchicine is an effective treatment for people with COVID-19 compared to placebo (a treatment that looks and tastes the same as colchicine but with no active ingredient) or usual care alone. We looked at people with moderate or severe disease being treated in hospital or with mild disease being treated in the community. We were particularly interested in the effects of colchicine on:

○ number of deaths; 

○whether people’s condition worsened or improved;

○ quality of life; 

○ serious and non-serious side effects 

 What did we do?

We searched for studies that compared colchicine together with usual care to usual care (plus/minus placebo). Studies could take place anywhere in the world and include people with mild or no symptoms, moderate or severe COVID-19, of any age, sex, or ethnicity.

We compared and summarised the results of the studies and rated our certainty in the evidence, based on factors such as study methods and sizes.

What did we find?

We identified four eligible randomised trials. Three included 11,525 hospitalised people and one included 4488 non-hospitalised people. For hospitalised people, the average age was 64 years, and for non-hospitalised people, the average age was 55 years. Two studies compared colchicine and usual care with usual care alone and 2 studies compared colchicine with usual care and placebo. None of the studies reported quality of life. We also found 17 ongoing studies and 11 completed but unpublished studies. 

Main results

Hospitalised people with moderate to severe COVID-19 (3 studies, 11,525 people)

○Colchicine probably does not reduce deaths in the 28 days after treatment (2 studies, 11,445 people).

○Colchicine probably does not prevent the worsening of patients’ condition (2 studies, 10,916 people) and probably does not improve it (1 study, 11,340 people). 

○We are very uncertain about the effect of colchicine on side effects and serious side effects (2 studies, 177 people).

Non-hospitalised people with no symptoms or mild COVID-19 (1 study, 4488 people)

○We are uncertain whether colchicine prevents deaths up to 28 days after treatment.

○Colchicine probably slightly reduces the risk of hospitalisation or death. 

○We are uncertain about the effect of colchicine on side effects, but it probably slightly reduces serious side effects.

What are the limitations of the evidence?

Our certainty in the evidence is limited. Two studies did not use a placebo, so everybody knew who was treated with colchicine, which could influence the results. There were too few events for non-hospitalised people, such as admissions to hospital and deaths, to be certain about the evidence. Studies used different ways to assess and report unwanted effects, so we could not combine studies into a single result to make a judgement.

How up to date is this evidence?

The evidence is up to date to 21 May 2021.

Editorial note: this is a living systematic review. We search for new evidence every week and update the review when we identify relevant new evidence. Refer to the Cochrane Database of Systematic Reviews for the current status of this review.

Authors' conclusions: 

Based on the current evidence, in people hospitalised with moderate to severe COVID-19 the use of colchicine probably has little to no influence on mortality or clinical progression in comparison to placebo or standard care alone. We do not know whether colchicine increases the risk of (serious) adverse events.

We are uncertain about the evidence of the effect of colchicine on all-cause mortality for people with asymptomatic infection or mild disease. However, colchicine probably results in a slight reduction of hospital admissions or deaths within 28 days, and the rate of serious adverse events compared with placebo.

None of the studies reported data on quality of life or compared the benefits and harms of colchicine versus other drugs, or different dosages of colchicine.

We identified 17 ongoing and 11 completed but not published RCTs, which we expect to incorporate in future versions of this review as their results become available.

Editorial note: due to the living approach of this work, we monitor newly published results of RCTs on colchicine on a weekly basis and will update the review when the evidence or our certainty in the evidence changes.

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