Efficacy and safety of topical and systemic medications: A systematic literature review informing the EULAR recommendations for the management of Sjögren's syndrome

Research output: Contribution to journalReview article


Objective To evaluate current evidence on the efficacy and safety of topical and systemic medications in patients with primary Sjögren syndrome (SjS) to inform European League Against Rheumatism treatment recommendations. Methods The MEDLINE, EMBASE and Cochrane databases were searched for case-control/prospective cohort studies, randomised controlled trials (RCTs) and systematic reviews. Results Current evidence in primary SjS patients fulfilling the 2002 criteria is based on the data from 9 RCTs, 18 prospective cohort studies and 5 case-control studies. Two Cochrane systematic literature reviews (SLRs) have reported that topical treatments for dry mouth and dry eye are safe and effective. Ocular cyclosporine A was safe and effective in two RCTs including 1039 patients with dry eye syndrome. Two Cochrane SLRs on serum tear drops and plugs showed inconsistency in possible benefits, both for symptoms and objective measures. Five RCTs reported significant improvements in oral dryness and salivary flow rates for pilocarpine and cevimeline. An RCT showed no significant placebo-differences for hydroxychloroquine 400 mg/day for the primary outcome (visual analogue scale (VAS) composite of dryness, fatigue and pain). We identified seven RCTs carried out in primary SjS patients. RCTs using infliximab, anakinra and baminercept found no placebo-differences for the primary outcomes. The two largest RCTs randomised 255 patients to receive rituximab or placebo and reported no significant results in the primary outcome (VAS composite), while prospective studies suggested efficacy in systemic disease. Conclusion The current evidence supporting the use of the main topical therapeutic options of primary SjS is solid, while limited data from RCTs are available to guide systemic therapies.


  • Pilar Brito-Zerón
  • Soledad Retamozo
  • Belchin Kostov
  • Chiara Baldini
  • Hendrika Bootsma
  • Salvatore De Vita
  • Thomas Dörner
  • Jacques Eric Gottenberg
  • Aike A. Kruize
  • Thomas Mandl
  • Wan Fai Ng
  • Raphaele Seror
  • Athanasios G. Tzioufas
  • Claudio Vitali
  • Simon Bowman
  • Xavier Mariette
  • Manuel Ramos-Casals
External organisations
  • Autonomous University of Barcelona
  • Institutd' Investigacions Biomèdiques August Pi iSunyer (IDIBAPS)
  • National University of Cordoba, Argentina
  • Polytechnic University of Catalonia
  • University of Pisa
  • University Medical Center Groningen
  • University Hospital 'Santa Maria della Misericordia'
  • Charité - University Medicine Berlin
  • University Hospital Of Strasbourg
  • University Medical Center Utrecht
  • Skåne University Hospital
  • NHS Foundation Trust
  • Bicêtre Hospital
  • University of Paris-Sud
  • National and Kapodistrian University of Athens
  • University Hospitals Birmingham
  • Hospital Clínic of Barcelona
  • Villa San Giuseppe Santo Stefano Riabilitazione, Como
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Rheumatology and Autoimmunity


  • multidisciplinary team-care, Sjøgren's syndrome, treatment
Original languageEnglish
Article numbere001064
JournalRMD Open
Issue number2
Publication statusPublished - 2019 Oct 28
Publication categoryResearch