title: Efficacy and safety of rituximab treatment in early primary Sjögren's syndrome: a prospective, multi-center, follow-up study.
abstract: BACKGROUND
  Primary Sjögren's syndrome (pSS) is an autoimmune disorder affecting exocrine glands; however, a subgroup of pSS patients experience systemic extra-glandular involvement leading to a worsening of disease prognosis. Current therapeutic options are mainly empiric and often translated by other autoimmune diseases. In the last few years growing evidence suggests that B-cell depletion by rituximab (RTX) is effective also in pSS. Patients with early active disease appear to be those who could benefit the most from RTX. The aim of this study was to investigate the efficacy and safety of RTX in comparison to disease modifying anti-rheumatic drugs (DMARDs) in early active pSS patients.
  
  
  METHODS
  Forty-one patients with early pSS and active disease (EULAR Sjogren's syndrome disease activity index, ESSDAI ≥ 6) were enrolled in the study. Patients were treated with either RTX or DMARDs in two different Rheumatology centers and followed up for 120 weeks. Clinical assessment was performed by ESSDAI every 12 weeks up to week 120 and by self-reported global disease activity pain, sicca symptoms and fatigue on visual analogic scales, unstimulated saliva flow and Schirmer's I test at week 12, 24, 48, 72, 96, and 120. Laboratory assessment was performed every 12 weeks to week 120. Two labial minor salivary gland (MSG) biopsies were obtained from all patients at the time of inclusion in the study and at week 120.
  
  
  RESULTS
  Our study demonstrated that RTX treatment results in a faster and more pronounced decrease of ESSDAI and other clinical parameters compared to DMARDs treatment. No adverse events were reported in the two groups. We also observed that RTX is able to reduce glandular infiltrate, interfere with B/T compartmentalization and consequently with the formation of ectopic lymphoid structures and germinal center-like structures in pSS-MSGs.
  
  
  CONCLUSIONS
  To our knowledge, this is the first study performed in a large cohort of early active pSS patients for a period of 120 weeks. We showed that RTX is a safe and effective agent to be employed in pSS patients with systemic, extra-glandular involvement. Furthermore, our data on pSS-MSGs provide additional biological basis to employ RTX in this disease.
authors.forename: Francesco
authors.initials: F
authors.lastname: Carubbi
authors.forename: Paola
authors.initials: P
authors.lastname: Cipriani
authors.forename: Alessandra
authors.initials: A
authors.lastname: Marrelli
authors.forename: Paola
authors.initials: P
authors.lastname: Benedetto
authors.forename: Piero
authors.initials: P
authors.lastname: Ruscitti
authors.forename: Onorina
authors.initials: O
authors.lastname: Berardicurti
authors.forename: Ilenia
authors.initials: I
authors.lastname: Pantano
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Liakouli
authors.forename: Saverio
authors.initials: S
authors.lastname: Alvaro
authors.forename: Alessia
authors.initials: A
authors.lastname: Alunno
authors.forename: Antonio
authors.initials: A
authors.lastname: Manzo
authors.forename: Francesco
authors.initials: F
authors.lastname: Ciccia
authors.forename: Roberto
authors.initials: R
authors.lastname: Gerli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Triolo
authors.forename: Roberto
authors.initials: R
authors.lastname: Giacomelli
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001706:Biopsy; D054377:Chemokine CXCL12 / Q000235:genetics; D054382:Chemokine CXCL13 / Q000235:genetics; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D011446:Prospective Studies; D019718:Receptors, CXCR4 / Q000235:genetics; D054380:Receptors, CXCR5 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000069283:Rituximab; D012469:Salivary Glands / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D057566:Self Report; D012859:Sjogren's Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; C095085:CXCR5 protein, human; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D019718:Receptors, CXCR4; D054380:Receptors, CXCR5; D000069283:Rituximab