title: Rituximab therapy for primary Sjögren's syndrome: an open-label clinical trial and mechanistic analysis.
abstract: OBJECTIVE
  To study the safety and clinical efficacy of rituximab therapy for primary Sjögren's syndrome, as well as to investigate its mechanisms.
  
  
  METHODS
  Patients with primary Sjögren's syndrome were enrolled in an open-label trial, were given rituximab (1 gm) infusions on days 1 and 15, and were monitored through week 52. The primary end point was safety, with secondary end points evaluating clinical and biologic efficacy. Blood was obtained for enumeration of lymphocyte subsets, measurement of serum autoantibody and BAFF levels, and analysis of gene expression.
  
  
  RESULTS
  Twelve female patients with primary Sjögren's syndrome were administered rituximab. They had a median age of 51 years (range 34-69 years) and a median disease duration of 8.0 years (range 2-18 years). We observed no unexpected toxicities from the rituximab therapy. Modest improvements were observed at week 26 in patient-reported symptoms of fatigue and oral dryness, with no significant improvement in the objective measures of lacrimal and salivary gland function. The recovery of blood B cells following the nadir from rituximab therapy was characterized by a predominance of transitional B cells and a lack of memory B cells. While blood B cell depletion was associated with an increase in serum BAFF levels, no significant changes were observed in the levels of serum anti-Ro/SSA, anti-La/SSB, and anti-type 3 muscarinic acetylcholine receptor autoantibodies or in the blood interferon signature.
  
  
  CONCLUSIONS
  In patients with primary Sjögren's syndrome, a single treatment course of rituximab was not associated with any unexpected toxicities and led to only modest clinical benefits despite effective depletion of blood B cells.
authors: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. stcla003@mc.duke.edu
authors: E William
authors: EW
authors: St Clair
authors: Marc C
authors: MC
authors: Levesque
authors: Eline T Luning
authors: ET
authors: Prak
authors: Frederick B
authors: FB
authors: Vivino
authors: Chacko J
authors: CJ
authors: Alappatt
authors: Meagan E
authors: ME
authors: Spychala
authors: Josiah
authors: J
authors: Wedgwood
authors: James
authors: J
authors: McNamara
authors: Kathy L
authors: KL
authors: Moser Sivils
authors: Lytia
authors: L
authors: Fisher
authors: Philip
authors: P
authors: Cohen
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood / Q000187:drug effects; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D018655:Lymphocyte Count; D008875:Middle Aged; D011446:Prospective Studies; D000069283:Rituximab; D012859:Sjogren's Syndrome / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D007155:Immunologic Factors; D000069283:Rituximab