title: Efficacy and safety of nonbiologic immunosuppressants in the treatment of nonrenal systemic lupus erythematosus: a systematic review.
abstract: OBJECTIVE
  To analyze the efficacy and safety of nonbiologic immunosuppressants in the treatment of nonrenal systemic lupus erythematosus (SLE).
  
  
  METHODS
  We conducted a sensitive literature search in Medline, Embase, and the Cochrane Central Register of Controlled Trials up to October 2011. The selection criteria were studies including adult patients with SLE, a treatment intervention with nonbiologic immunosuppressants, a placebo or active comparator group, and outcome measures assessing efficacy and/or safety. Meta-analyses, systematic reviews, clinical trials, and cohort studies were included. The quality of each study was evaluated using Jadad’s scale and the Oxford Levels of Evidence.
  
  
  RESULTS
  In total, 158 of the 2,827 initially found articles were selected for detailed review; 65 studies fulfilled the predetermined criteria. Overall, the studies were low quality, with only 11 randomized controlled trials (RCTs). Cyclophosphamide demonstrated efficacy for neuropsychiatric SLE, preventing relapses with an 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 cyclosporin A) demonstrated efficacy in reducing nonrenal activity and flares with a steroid-sparing effect, although only on occasion in non–placebo-controlled RCTs of small numbers of patients.
  
  
  CONCLUSIONS
  Several immunosuppressants demonstrated their safety and efficacy in nonrenal SLE. A specific drug for each particular manifestation cannot be recommended, although cyclophosphamide may be used in more severe cases, and methotrexate may be the first option in most cases of moderately active SLE. High-quality RCTs of larger numbers of patients are needed.
authors.forename: José M
authors.initials: JM
authors.lastname: Pego-Reigosa
authors.forename: Tatiana
authors.initials: T
authors.lastname: Cobo-Ibáñez
authors.forename: Jaime
authors.initials: J
authors.lastname: Calvo-Alén
authors.forename: Estíbaliz
authors.initials: E
authors.lastname: Loza-Santamaría
authors.forename: Anisur
authors.initials: A
authors.lastname: Rahman
authors.forename: Santiago
authors.initials: S
authors.lastname: Muñoz-Fernández
authors.forename: Íñigo
authors.initials: Í
authors.lastname: Rúa-Figueroa
mesh_terms: D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents