title: Cyclophosphamide versus methylprednisolone for treating neuropsychiatric involvement in systemic lupus erythematosus.
abstract: BACKGROUND
  Neuropsychiatric involvement in systemic lupus erythematosus (SLE) is complex and it is an important cause of morbidity and mortality. Management of nervous system manifestations of SLE remains unsatisfactory. This is an update of a Cochrane review first published in 2000 and previously updated in 2006.
  
  
  OBJECTIVE
  To assess the benefits and harms of cyclophosphamide and methylprednisolone in the treatment of neuropsychiatric manifestations of SLE.
  
  
  METHODS
  We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, SCOPUS and WHO up to and including June 2012. We sought additional articles through handsearching in relevant journals as well as contact with experts. There were no language restrictions.
  
  
  METHODS
  We included all randomised controlled trials that compared cyclophosphamide to methylprednisolone in patients with SLE of any age and gender and presenting with any kind of neuropsychiatric manifestations.
  
  
  METHODS
  Two review authors independently extracted, assessed and cross-checked data. We produced a 'Summary of findings' table. We presented dichotomous data as risk ratios (RRs) with 95% confidence intervals (CIs).
  
  
  RESULTS
  We did not include any new trials in this update. One randomised controlled trial of 32 patients is included. Concerning risk of bias, generation of the allocation sequence was at low risk; however, allocation concealment, blinding and selective reporting were at high risk. Treatment response, defined as 20% improvement from basal conditions by clinical, serological and specific neurological measures, 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 to 3.73). This was statistically significant and the number needed to treat for an additional beneficial outcome (NNTB) of treatment response is three. We found no statistically significant differences between the groups in damage index measurements (Systemic Lupus International Collaborating Clinics (SLICC)). The median SLE Disease Activity Index (SLEDAI) rating favoured the cyclophosphamide group. Cyclophosphamide use was associated with a reduction in prednisone requirements. All the patients in the cyclophosphamide group had electroencephalographic improvement but there was no statistically significant difference in decrease between groups in the number of monthly seizures. No statistically significant differences in adverse effects, including mortality, were reported between the groups.
  
  
  CONCLUSIONS
  This systematic review found one randomised controlled trial with a small number of patients in the different clinical subgroups of neurological manifestation. There is very low-quality evidence that cyclophosphamide is more effective in reducing symptoms of neuropsychiatric involvement in SLE compared with methylprednisolone. However, properly designed randomised controlled trials that involve large numbers of individuals, with explicit clinical and laboratory diagnostic criteria, sufficient duration of follow-up and description of all relevant outcome measures, are necessary to guide practice. As we did not find any new trials to include in this review at update, the conclusions of the review did not change.
authors: Rheumatology/Internal Medicine and Therapeutics, Universidade Federal de São Paulo, São Paulo, Brazil. vmoca@uol.com.br
authors: Virginia
authors: V
authors: Fernandes Moça Trevisani
authors: Aldemar A
authors: AA
authors: Castro
authors: João
authors: J
authors: Ferreira Neves Neto
authors: Alvaro N
authors: AN
authors: Atallah
mesh_terms: 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*; D016032:Randomized Controlled Trials as Topic; D012640:Seizures / Q000188:drug therapy / Q000209:etiology
chemical_list: D007166:Immunosuppressive Agents; D018696:Neuroprotective Agents; D003520:Cyclophosphamide; D008775:Methylprednisolone