Cyclophosphamide versus methylprednisolone for treating neuropsychiatric involvement in systemic lupus erythematosus.
BACKGROUND
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.


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


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.


METHODS
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).


METHODS
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.


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.


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.
Trevisani
V F M
VF
Universidade Federal de Sao Paulo, Escola Paulista de Medicina, Rua Pedro de Toledo 598, Sao Paulo, Brazil, 04024 900. cochrane.dmed@epm.br
Castro
A A
AA
Neves Neto
J F
JF
Atallah
A N
AN
D003520:Cyclophosphamide / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000188:drug therapy; D008775:Methylprednisolone / Q000627:therapeutic use*; D019965:Neurocognitive Disorders / Q000188:drug therapy* / Q000209:etiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012640:Seizures / Q000188:drug therapy / Q000209:etiology
D007166:Immunosuppressive Agents; D018696:Neuroprotective Agents; D003520:Cyclophosphamide; D008775:Methylprednisolone