title: Rituximab Effectiveness and Safety for Treating Primary Sjögren's Syndrome (pSS): Systematic Review and Meta-Analysis.
abstract: BACKGROUND
  Primary Sjögren's Syndrome (pSS) is a systemic autoimmune disease that involves the exocrine glands and internal organs. pSS leads to destruction and loss of secretory function due to intense lymphoplasmacytic infiltration. Therapeutic options include mainly symptomatic and supportive measures, and traditional immunosuppressant drugs have shown no effectiveness in randomized trials. Rituximab (RTX) is a chimeric antibody anti-CD20 that leads to B cell depletion by diverse mechanisms. There is evidence that this drug may be effective for treating pSS. The objective of this systematic review was to evaluate Rituximab effectiveness and safety for treating pSS.
  
  
  RESULTS
  We conducted a systematic review of RCTs published until December 2015, with no language restriction. We registered a protocol on Plataforma Brasil (40654814.6.0000.5505) and developed search strategies for the following scientific databases: MEDLINE, EMBASE, CENTRAL and LILACS. We included adults with established pSS diagnosis and considered the use of Rituximab as intervention and the use of other drugs or placebo as control. Four studies met our eligibility criteria: three with low risk of bias and one with uncertain risk of bias. The total number of participants was 276 (145 RTX, 131 placebo). We assessed the risk of bias of each included study and evaluated the following as primary outcomes: lacrimal gland function, salivary gland function, fatigue improvement and adverse events. We found no significant differences between the groups in the Schirmer test at week 24 meta-analysis (MD 3.59, 95% CI -2.89 to 10.07). Only one study evaluated the lissamine green test and reported a statistically significant difference between the groups at week 24 (MD -2.00, 95% CI -3.52 to -0.48). There was a significant difference between the groups regarding salivary flow rate (MD 0.09, 95% CI 0.02 to 0.16) and improvement in fatigue VAS at weeks 6 (RR 3.98, 95% CI 1.61 to 9.82) and week 16 (RR 3.08, 95% CI 1.21 to 7.80).
  
  
  CONCLUSIONS
  According to moderate quality evidence, the treatment with a single RTX course in patients with SSp presents discrete effect for improving lacrimal gland function. Low-quality evidence indicates the potential of this drug for improving salivary flow. According to low quality evidence, no differences were observed in the evaluation after 24 weeks regarding fatigue reduction (30% VAS), serious adverse events occurrence, quality of life improvement and disease activity. With a very low level of evidence, there was no improvement in oral dryness VAS evaluation.
authors.affiliation: Department of Evidence-Based Medicine, São Paulo Federal University (UNIFESP), São Paulo, Brazil.
authors.forename: Francine Bertolais do Valle
authors.initials: FB
authors.lastname: Souza
authors.affiliation: Department of Evidence-Based Medicine, São Paulo Federal University (UNIFESP), São Paulo, Brazil.
authors.forename: Gustavo José Martiniano
authors.initials: GJ
authors.lastname: Porfírio
authors.affiliation: Department of Evidence-Based Medicine, São Paulo, Federal University (UNIFESP), São Paulo, Brazil.
authors.forename: Brenda Nazaré Gomes
authors.initials: BN
authors.lastname: Andriolo
authors.affiliation: Department of Evidence-Based Medicine, São Paulo Federal University (UNIFESP), São Paulo, Brazil.
authors.forename: Julia Vajda de
authors.initials: JV
authors.lastname: Albuquerque
authors.affiliation: Department of Evidence-Based Medicine, São Paulo Federal University (UNIFESP) São Paulo, Brazil.|Department of Rheumatology, Santo Amaro University (UNISA), São Paulo, Brazil.
authors.forename: Virginia Fernandes Moça
authors.initials: VF
authors.lastname: Trevisani
mesh_terms: D006801:Humans; D010919:Placebos; D017594:Publication Bias; D000069283:Rituximab / Q000009:adverse effects* / Q000627:therapeutic use*; D012859:Sjogren's Syndrome / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D010919:Placebos; D000069283:Rituximab