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. Objectives: To assess the benefits and harms of cyclophosphamide and methylprednisolone in the treatment of neuropsychiatric manifestations of SLE. Search 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. Selection criteria: 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. Data collection and analysis: 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). Main 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. Authors' 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.