Background Different studies suggest that Rituximab (RTX) may be effective in lupus nephritis treatment. Nevertheless, systemic lupus erythematosus (SLE) is a heterogeneous disease with non-renal manifestations in which RTX has being used.

Objectives To systematically review the published evidence regarding the efficacy and safety of RTX in non-renal manifestations of SLE.

Methods We systematically searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials up to October 2011 using a comprehensive search strategy for RTX, SLE, efficacy and safety (mesh terms and text words). Selection criteria: a) adults patients with SLE; b) RTX treatment; c) outcomes in relation to efficacy like clinical improvement, remission, flares, steroid-sparing effect, etc. ; and/ or d) adverse events. Meta-analysis, systematic literature reviews, randomized control trials (RCT), open clinical trials, and cohort studies were included. Studies about lupus nephritis, cutaneous LE, paediatric SLE and basic science were excluded. Title and abstract selection and subsequent detailed review of selected articles were independently performed by two reviewers. A hand search was completed by reviewing the references of the included studies. The quality of the selected studies was graded using the Oxford Levels of Evidence Scale, and Jadad´s scale in case of RCT.

Results The search strategy identified 2,468 potentially relevant articles, of which 158 were selected for full paper review. Twenty-two articles were eventually included in the analysis and 1 identified by hand search. The selection included 1 RCT and 1 exploratory analyses of that RCT, 2 open trials, and 19 cohort studies, which analyzed 1,015 patients. Between 77-100% of patients were women with active disease refractory to steroids and/ or immunosuppressants. Follow-up range was of 2-48 months. Patients with non- renal and renal manifestations at once were identified in 82% of the studies, in the remainder of the studies, patients only showed non-renal disease. The most frequent non-renal manifestations were: musculoskeletal, mucocutaneous, hematologic, neurological, and immunologic (C3, C4 and anti ds DNA). Although the variability in the study design, regimens and doses of treatment, and outcomes, most patients on RTX showed improvement in the non-renal manifestations with a steroid-sparing effect. Few major adverse events were reported, being infusion reactions and infections the most frequent ones.

Conclusions In patients with active SLE and non-renal manifestations, RTX is safe and effective to improve disease activity, induce remission, reduce the dosage of corticosteroids, reduce levels of anti ds DNA, and in increasing levels of complement. However, relapse of disease is significant in the long-term (level of evidence 2b-C, grade of recommendation B).

Disclosure of Interest None Declared