title: Treatment of active lupus nephritis with the novel immunosuppressant 15-deoxyspergualin: an open-label dose escalation study.
abstract: BACKGROUND
  As the immunosuppressive potency of 15-deoxyspergualin (DSG) has been shown in the therapy of renal transplant rejection and Wegener's granulomatosis, the intention of this study was to evaluate the safety of DSG in the therapy of lupus nephritis (LN).
  
  
  METHODS
  Patients with histologically proven active LN after prior treatment with at least one immunosuppressant were treated with 0.5 mg/kg normal body weight/day DSG, injected subcutaneously for 14 days, followed by a break of one week. These cycles were repeated to a maximum of nine times. Doses of oral corticosteroids were gradually reduced to 7.5 mg/day or lower by cycle 4. Response was measured according to a predefined decision pattern. The dose of DSG was adjusted depending on the efficacy and side effects.
  
  
  RESULTS
  A total of 21 patients were included in this phase-I/II study. After the first DSG injection, one patient was excluded from the study due to renal failure. Five patients dropped out due to adverse events or serious adverse events including fever, leukopenia, oral candidiasis, herpes zoster or pneumonia. Eleven out of 20 patients achieved partial (4) or complete responses (7), 8 were judged as treatment failures and 1 patient was not assessable. Twelve patients completed all nine cycles; in those patients, proteinuria decreased from 5.88 g/day to 3.37 g/day (P = 0.028), Selena-SLEDAI (Safety of Estrogens in Lupus Erythematosus-National Assessment-systemic lupus erythematosus disease activity index) decreased from 17.6 to 11.7. In 13 out of 20 patients, proteinuria decreased by at least 50%; in 7 patients to less than 1 g/day.
  
  
  CONCLUSIONS
  Although the number of patients was small, we could demonstrate that DSG provides a tolerably safe treatment for LN. The improvement in proteinuria encourages larger controlled trials.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00709722.
authors.affiliation: Division of Rheumatology, University Hospital Heidelberg, INF410, 69120 Heidelberg, Germany. hannes.Lorenz@med.uni-heidelberg.de
authors.forename: Hanns-Martin
authors.initials: HM
authors.lastname: Lorenz
authors.forename: Wilhelm H
authors.initials: WH
authors.lastname: Schmitt
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tesar
authors.forename: Ulf
authors.initials: U
authors.lastname: Müller-Ladner
authors.forename: Ingo
authors.initials: I
authors.lastname: Tarner
authors.forename: Ingeborg A
authors.initials: IA
authors.lastname: Hauser
authors.forename: Falk
authors.initials: F
authors.lastname: Hiepe
authors.forename: Tobias
authors.initials: T
authors.lastname: Alexander
authors.forename: Heike
authors.initials: H
authors.lastname: Woehling
authors.forename: Kyuichi
authors.initials: K
authors.lastname: Nemoto
authors.forename: Peter A
authors.initials: PA
authors.lastname: Heinzel
mesh_terms: D000328:Adult; D005260:Female; D006146:Guanidines / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008181:Lupus Nephritis / Q000188:drug therapy*; D008297:Male; D010865:Pilot Projects; D055815:Young Adult
chemical_list: D006146:Guanidines; D007166:Immunosuppressive Agents; C037258:gusperimus