This is not the most recent version of the article. View current version (28 FEB 2013)

Intervention Review

Cyclophosphamide versus methylprednisolone for treating neuropsychiatric involvement in systemic lupus erythematosus

  1. Virginia Fernandes Moça Trevisani1,*,
  2. Aldemar A Castro2,
  3. João JFNN Ferreira Neves Neto3,
  4. Álvaro N Atallah4

Editorial Group: Cochrane Musculoskeletal Group

Published Online: 19 APR 2006

Assessed as up-to-date: 20 FEB 2006

DOI: 10.1002/14651858.CD002265.pub2

How to Cite

Trevisani VFM, Castro AA, Ferreira Neves Neto JJFNN, Atallah ÁN. Cyclophosphamide versus methylprednisolone for treating neuropsychiatric involvement in systemic lupus erythematosus. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD002265. DOI: 10.1002/14651858.CD002265.pub2.

Author Information

  1. 1

    UNISA (Santo Amaro University)/UNIFESP (Paulista Medicine School), Rheumatology/Internal Medicine and Therapeutics, Jardim Marajoara, Sao Paulo, Brazil

  2. 2

    State University of Heath Science, Department of Public Health, Maceió, Alagoas, Brazil

  3. 3

    Federal University of São Paulo, Surgery, São Paulo, Lapa, Brazil

  4. 4

    Universidade Federal de São Paulo / Escola Paulista de Medicina, Brazilian Cochrane Centre, São Paulo, SP, Brazil

*Virginia Fernandes Moça Trevisani, Rheumatology/Internal Medicine and Therapeutics, UNISA (Santo Amaro University)/UNIFESP (Paulista Medicine School), Rua Marie Satzke 119, Jardim Marajoara, Sao Paulo, 04664-150, Brazil.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 19 APR 2006


This is not the most recent version of the article. View current version (28 FEB 2013)



  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要


Neuropsychiatric involvement in systemic lupus erythematosus is complex and several clinical presentations are related to this disease such as: convulsions, chronic headache, transverse myelitis, vascular brain disease, psychosis and neural cognitive dysfunction. This systematic review is an update of a review performed in 2000.


To assess the efficacy and safety of cyclophosphamide and methylprednisolone in the treatment of neuropsychiatric manifestations of systemic lupus erythematosus.

Search methods

We searched EMBASE, LILACS, Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE up to and including May 2005. Additional articles were sought through handsearching in relevant journals. There were no language restrictions.

Selection criteria

All randomised controlled trials that compared cyclophosphamide to methylprednisolone were included. Patients of any age and gender were included as long as they fulfilled the criterion of the American College of Rheumatology for the diagnosis of systemic lupus erythematosus and presented with any one of the following neuropsychiatric events: convulsions, organic brain syndrome and cranial neuropathy. Outcome measures included the following: a) overall mortality (primary event); b) motor and psychiatric deficit (primary event); c) clinical improvement (secondary event).

Data collection and analysis

Data was independently extracted by two reviewers and cross-checked. The methodological quality of each trial was assessed by the same two reviewers. Details of the randomisation (generation and concealment), blinding, and the number of patients lost to follow-up were recorded. Dichotomous data was presented as relative risks with corresponding 95% confidence intervals and a clinical relevance table was produced.

Main results

We found one randomised controlled trial of 32 patients comparing cyclophosphamide versus methylprednisolone for the treatment of neuropsychiatric involvement in the systemic lupus erythematosus. A significantly greater number of people responded to treatment in the cyclophosphamide group. Treatment response was found in 94.7% (18/19) of patients using cyclophosphamide compared with 46.2% (6/13) in the methylprednisolone group at 24 months (RR 2.05, 95% CI 1.13, 3.73) The NNT for response to treatment is 2. Cyclophosphamide use was associated with a reduction in prednisone requirements. A significant decrease in the number seizures per month was observed in the cyclophosphamide group. All the patients in the cyclophosphamide group had electroencephalographic improvement. No significant differences in adverse effects between the groups were found. It was not possible to extract more data from the study because there was a small number of patients in the others clinical subgroups of neurological manifestations and the authors did not provide sufficient information for data extraction.

Authors' conclusions

This systematic review found one randomised controlled trial with a small number of patients in the different clinical subgroups of neurological manifestation. It seems that cyclophosphamide is more effective in the treatment of neuropsychiatric involvement in systemic erythematosus lupus compared with methylprednisolone. However, properly designed randomised controlled trials that involve large, representative numbers of individuals, with explicit clinical and laboratory diagnosis criteria, sufficient duration of follow-up and description of all relevant outcome measures are necessary to guide practice.


Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Cyclophosphamide versus methylprednisolone for lupus

Does cyclophosphamide work to treat central nervous system lupus (neuropsychiatric lupus)?

One study of moderate quality provides the best evidence we have to answer this question. The study tested 32 people who had central nervous system lupus. The study compared people who took cyclosphosphamide by IV (intravenous or through a vein) to people who took steroids (methylprednisolone by IV). All people took steroid pills (prednisone) at the beginning of the study and the amount was decreased over the study. The study lasted 2 years.

What is central nervous system lupus and how could cyclophosphamide help?
Systemic lupus erythematosus (SLE) or simply 'lupus' is a group of diseases in which the body's immune system attacks the body. In CNS lupus (central nervous system lupus) the body may have attacked and damaged the cells in the brain and spine. This damage may cause a person to have convulsions/seizures, chronic headaches, confusion and psychosis. Drugs such as corticosteroids (prednisone or methylprednisolone) are usually used for lupus to decrease inflammation and control the immune system. Immunosuppressive agents or cytotoxics such as cyclophosphamide (CTX or Cytoxan) may also be used. These drugs can be given by IV (intravenous or through your veins) or as pills. Unfortunately, it has not been clear whether these drugs improve the symptoms of CNS lupus and what the side effects are.

What did the studies show?
More people who took cyclophosphamide improved than people who took methylprednisolone.
- 95 out of 100 people had at least a 20% improvement in symptoms with cyclophosphamide

- 46 out of 100 people had at least a 20% improvement in symptoms with methylprednisolone

Disease activity, seizures, CNS damage also decreased more with cyclophosphamide.

After 6 months of treatment, people who took cyclophosphamide took less prednisone pills than people who took methylprednisolone. And at the end of two years, it seemed that more people who took cyclophosphamide stayed on their treatment than the people who took methylprednisolone.

Were there any side effects?
Side effects, such as infections, high blood sugar and high blood pressure, pancreatitis and death occurred about the same amount in people who took cyclophosphamide or methylprednisolone.

What is the bottom line?
There is "silver" level evidence ( that cyclophosphamide may improve symptoms of central nervous system (neuropsychiatric) lupus more than methylprednisolone. It also does not appear to increase side effects. The study in this review was small and more studies are needed.



  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要







搜尋EMBASE, LILACS, Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE (到2005年5月),同時手動搜尋所選文章之參考文獻。


所有比較Cyclophosphamide與methylprednisolone治療神經精神系統侵患之紅斑性狼瘡的隨機對照研究,同時至少有評估下列一種事件:痙攣convulsions、器質性腦徵候群organic brain syndrome、腦神經病變cranial neuropathy。結果指標包括 a) 整體死亡率(主要指標)) 運動及精神缺損 (主要指標)) 臨床改善 (次要指標)。




1個隨機對照研究包含32例病患於分析中。Cyclophosphamide比methylprednisolone組之有效反應病患多。在24個月Cyclophosphamide組有反應病患94.7% (18/19),methylprednisolone組有反應病患46.2% 6/13) (RR 2.05, 95% CI 1.13, 3.73),NNT是2。 Cyclophosphamide減少prednisone使用量,且減少每月癲癇次數,所有clophosphamide組腦波有改善。兩組之副作用無顯著差異。因樣本數少,無法做細項分析。


本段: 這個系統性文獻回顧發現一個在各個神經表現次群體中有少量病人的隨機對照試驗。Cyclophosphamide對於系統性紅斑狼瘡較methylprednisolone有效。不過,需要設計良好的隨機對照試驗:具有代表性的病患數量、明確的臨床與實驗室診斷準則、充足的後續追蹤並且詳述所有重要結果測量方式,以引導實務操作。



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


■cyclophosphamide是否能有效治療中樞神經系統狼瘡? 一個中等品質的研究提供了我們目前回答此問題的最佳證據。該研究測試了32位神經精神系統紅斑性狼瘡患者。該研究比較靜脈注射cyclosphosphamide病人與注射類固醇(靜脈注射methylprednisolone)病人。所有的病人在研究開始時皆服用了類固醇藥丸(prednisone),而數量隨著研究期間減少,該研究進行了2年。 ■什麼是中樞神經系統狼瘡,而cyclophosphamide又為何能有所助益 系統性紅斑性狼瘡(SLE)或是單純狼瘡是一種免疫系統侵犯身體的疾病。患有中樞神經系統狼瘡,其自體可能侵犯並損害大腦與脊椎細胞。這樣的損害會造成病人發生抽痙/痙攣、慢性頭痛、意識不清、以及精神病。Corticosteroid等藥物(prednisone或methylprednisolone)通常用於狼瘡,以減少發炎並且控制免疫系統。也可以使用免疫抑制劑或細胞毒殺藥劑如cyclophosphamide (CTX或Cytoxan)。這些藥物可以透過靜脈注射(靜脈內注射或透過血管)或是藥丸施予。很不幸的,對於這些藥物是否能夠改善CNS狼瘡症狀,以及其副作用至今仍不清楚。 ■研究顯示什麼? 使用cyclophosphamide的病人較使用methylprednisolone的病人改善來得多。使用cyclophosphamide者,每100個病人當中即有95位至少達到20% 症狀改善;使用methylprednisolone者,每100個病人當中有46位至少達到20% 症狀改善。使用cyclophosphamide也更能減少疾病活動度分數、痙攣、CNS帶來的損害。經過6個月治療,採用cyclophosphamide的病人相較於採用methylprednisolone的病人服用較少的prednisone藥丸。而在兩年後,仍採用cyclophosphamide治療者多於仍採用methylprednisolone治療者。 ■是否有任何副作用呢? 副作用,如感染、高血糖和高血壓、胰臟炎以及死亡事件的數量在服用cyclophosphamide或methylprednisolone的病患身上大致相同。 ■ 臨床重要結論為何?銀級證據顯示cyclophosphamide相較於methylprednisolone更能改善中樞神經系統狼瘡(神經性精神病)症狀。而它似乎也不會增加副作用。本回顧當中的研究樣本數較小,需要更多的研究。