Background To date, few randomised clinical trials (RCTs) have analyzed the effect of the available therapies on non-renal manifestations of SLE. Specifically, there is limited evidence on the efficacy of non-biologic immunosuppressants for the treatment of non-renal manifestations of the disease. In spite of that, several of those manifestations are frequently treated with off-label medications.
Objectives To systematically review the available literature regarding the efficacy and safety of non-biologic immunosuppressive therapies in the treatment of non-renal systemic lupus erythematosus (SLE).
Methods Systematic review performed by members of the Systemic Autoimmune Diseases Study Group and Research Unit of the Spanish Society of Rheumatology. We conducted a sensitive literature search in Medline, Embase, and the Cochrane Central Register of Controlled Trials up to October 2011. Selection criteria: a) population: adult patients with SLE, b) intervention: treatment with non-biologic immunosuppressant, c) comparator: placebo or active comparator, d) outcome measures assessing efficacy: non-renal manifestations, scores by activity indices, SLE flares, steroid-sparing effect, etc., and e) outcome measures assessing safety: infections, cardiovascular events, malignancies, etc. Meta-analyses, systematic reviews, clinical trials and cohort studies were included. The quality of each study was evaluated using the Jadad’s scale and Oxford Levels of Evidence.
Results One hundred fifty-eight articles were selected for detailed review of the 2,827 initially found. Finally, 63 articles fulfilled the predetermined criteria. Overall, they were low-quality studies with only 11 RCTs. Cyclophosphamide demonstrated efficacy for neuropsychiatric SLE preventing relapses with additional steroid-sparing effect although its use was associated with cumulative damage, development of cervical intraepithelial neoplasia and ovarian failure. Other immunosuppressants (azathioprine, methotrexate, leflunomide, mycophenolate mofetil and cyclosporine A) demonstrated efficacy in reducing non-renal activity and flares with a steroid-sparing effect, although on occasions in non placebo-controlled RCTs of small number of patients.
Conclusions Several immunosuppressants have demonstrated their safety and efficacy in non-renal SLE. A specific drug for each particular manifestation cannot be recommended although cyclophosphamide may be kept to be used in more severe cases and methotrexate may be the first option in most cases of moderately active SLE. High-quality RCTs of a larger number of patients are needed
Disclosure of Interest None Declared