title: Prospective observational single-centre cohort study to evaluate the effectiveness of treating lupus nephritis with rituximab and mycophenolate mofetil but no oral steroids.
abstract: OBJECTIVE
  Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE). All current treatment regimens include oral steroids, which are associated with severe adverse events and long-term damage. We have piloted a steroid-avoiding protocol (rituxilup) for the treatment of biopsy-proven active International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III, IV, or class V LN.
  
  
  METHODS
  We report the findings from the first 50 consecutive patients, treated with 2 doses of rituximab (1 g) and methyl prednisolone (500 mg) on days 1 and 15, and maintenance treatment of mycophenolate mofetil. Patients on maintenance steroids or with life-threatening SLE or requiring dialysis were excluded. Renal remission was defined as serum creatinine no greater than 15% above baseline; complete biochemical remission (CR) was defined as urine protein : creatinine ratio (PCR)<50 mg/mmol or partial remission (PR) if PCR>50 mg/mmol but non-nephrotic and >50% reduction.
  
  
  RESULTS
  A total of 45 (90%) patients achieved CR or PR by a median time of 37 weeks (range 4-200). Overall, 72% (n=36) achieved CR (median time 36 weeks (11-58)) and a further 18% (n=9) achieved persistent PR (median time 32 weeks (19-58)). By 52 weeks, CR and PR had been achieved in 52% (n=26) and 34% (n=17) respectively. In all, 12 relapses occurred in 11 patients, at a median time of 65.1 weeks (20-112) from remission. A total of 6/50 patients had systemic flares. Of the 45 responders, only 2 required >2 weeks of oral steroids. Adverse events were infrequent; 18% were admitted, 10% for an infective episode.
  
  
  CONCLUSIONS
  The rituxilup cohort demonstrates that oral steroids can be safely avoided in the treatment of LN. If findings are confirmed, it could mark a step change in the approach to the treatment of LN.
authors.affiliation: Imperial College NHS Healthcare Trust Lupus Centre, Hammersmith Hospital, London, UK.
authors.forename: Marie B
authors.initials: MB
authors.lastname: Condon
authors.forename: Damien
authors.initials: D
authors.lastname: Ashby
authors.forename: Ruth J
authors.initials: RJ
authors.lastname: Pepper
authors.forename: H Terence
authors.initials: HT
authors.lastname: Cook
authors.forename: Jeremy B
authors.initials: JB
authors.lastname: Levy
authors.forename: Megan
authors.initials: M
authors.lastname: Griffith
authors.forename: Tom D
authors.initials: TD
authors.lastname: Cairns
authors.forename: Liz
authors.initials: L
authors.lastname: Lightstone
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D015331:Cohort Studies; D003401:Creatine / Q000097:blood; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008181:Lupus Nephritis / Q000188:drug therapy*; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011446:Prospective Studies; D011507:Proteinuria; D012074:Remission Induction; D000069283:Rituximab; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007166:Immunosuppressive Agents; D000069283:Rituximab; D009173:Mycophenolic Acid; D003401:Creatine; D008775:Methylprednisolone
keywords: B cells; Corticosteroids; Lupus Nephritis; Treatment