Cyclophosphamide versus methylprednisolone for treating neuropsychiatric involvement in systemic lupus erythematosus

  • Review
  • Intervention


  • Virginia Fernandes Moça Trevisani,

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

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  • Aldemar A Castro,

    1. State University of Heath Science, Department of Public Health, Maceió, Alagoas, Brazil
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  • João JFNN Ferreira Neves Neto,

    1. Federal University of São Paulo, Surgery, São Paulo, Lapa, Brazil
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  • Álvaro N Atallah

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

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.