title: B cell depletion with rituximab in patients with diffuse cutaneous systemic sclerosis.
abstract: OBJECTIVE
  To determine the safety of rituximab, to provide preliminary data regarding the potential efficacy of rituximab, and to investigate the effects of rituximab on autoimmunity and fibrosis in patients with diffuse cutaneous systemic sclerosis (dcSSc).
  
  
  METHODS
  Fifteen patients with dcSSc, all of whom experienced their first non-Raynaud's disease-associated disease manifestation within 18 months of trial entry, were recruited to receive 2 intravenous doses of rituximab (1,000 mg), administered 2 weeks apart. Safety, clinical, and exploratory outcomes were evaluated at baseline and at 6 months. The primary outcome was the change in the modified Rodnan skin thickness score (MRSS) at 6 months compared with baseline.
  
  
  RESULTS
  Adverse events included frequent infusion reactions and rare infections (urinary tract infection and dental abscess occurred in 1 patient each). The mean change in the MRSS between baseline and 6 months was not significant. Results of pulmonary function tests and other measures of major organ involvement were stable. The modest B cell infiltrates that were present in most skin biopsy specimens at baseline were completely depleted at 6 months in most patients. Autoantibody titers showed only modest and variable changes after treatment.
  
  
  CONCLUSIONS
  In this pilot study, treatment with rituximab appeared to be safe and well tolerated among patients with dcSSc. Rituximab treatment resulted in both depletion of circulating B cells and depletion of dermal B cells but had little effect on the levels of SSc-associated autoantibodies. Rituximab treatment did not appear to result in a significant beneficial effect on skin disease. The potential efficacy of rituximab in other organs such as the lung could not be clearly evaluated in this small open-label trial.
authors.affiliation: Boston University School of Medicine, Boston, Massachusetts 02118, USA. lafyatis@bu.edu
authors.forename: Robert
authors.initials: R
authors.lastname: Lafyatis
authors.forename: Eugene
authors.initials: E
authors.lastname: Kissin
authors.forename: Michael
authors.initials: M
authors.lastname: York
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Farina
authors.forename: Kerry
authors.initials: K
authors.lastname: Viger
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Fritzler
authors.forename: Peter A
authors.initials: PA
authors.lastname: Merkel
authors.forename: Robert W
authors.initials: RW
authors.lastname: Simms
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007275:Injections, Intravenous; D007958:Leukocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012129:Respiratory Function Tests; D000069283:Rituximab; D045743:Scleroderma, Diffuse / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D012867:Skin / Q000187:drug effects / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D007155:Immunologic Factors; D000069283:Rituximab