title: Randomized Controlled Trial of Rituximab and Cost-Effectiveness Analysis in Treating Fatigue and Oral Dryness in Primary Sjögren's Syndrome.
abstract: To investigate whether rituximab, an anti-B cell therapy, improves symptoms of fatigue and oral dryness in patients with primary Sjögren's syndrome (SS).
  
  
  
  We conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial that included health economic analysis. Anti-Ro-positive patients with primary SS, symptomatic fatigue, and oral dryness were recruited from 25 UK rheumatology clinics from August 2011 to January 2014. Patients were centrally randomized to receive either intravenous (IV) placebo (250 ml saline) or IV rituximab (1,000 mg in 250 ml saline) in 2 courses at weeks 0, 2, 24, and 26, with pre- and postinfusion medication including corticosteroids. The primary end point was the proportion of patients achieving a 30% reduction in either fatigue or oral dryness at 48 weeks, as measured by visual analog scale. Other outcome measures included salivary and lacrimal flow rates, quality of life, scores on the European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient Reported Index and EULAR Sjögren's Syndrome Disease Activity Index, symptoms of ocular and overall dryness, pain, globally assessed disease activity, and cost-effectiveness.
  
  
  
  All 133 patients who were randomized to receive placebo (n = 66) or rituximab (n = 67) were included in the primary analysis. Among patients with complete data, 21 of 56 placebo-treated patients and 24 of 61 rituximab-treated patients achieved the primary end point. After multiple imputation of missing outcomes, response rates in the placebo and rituximab groups were 36.8% and 39.8%, respectively (adjusted odds ratio 1.13 [95% confidence interval 0.50, 2.55]). There were no significant improvements in any outcome measure except for unstimulated salivary flow. The mean ± SD costs per patient for rituximab and placebo were £10,752 ± 264.75 and £2,672 ± 241.71, respectively. There were slightly more adverse events (AEs) reported in total for rituximab, but there was no difference in serious AEs (10 in each group).
  
  
  
  The results of this study indicate that rituximab is neither clinically effective nor cost-effective in this patient population.
authors.affiliation: University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Bowman
authors.affiliation: University of Leeds, Leeds, UK.
authors.forename: Colin C
authors.identifier: 0000-0002-9788-840X
authors.initials: CC
authors.lastname: Everett
authors.affiliation: University of Leeds, Leeds, UK.
authors.forename: John L
authors.initials: JL
authors.lastname: O'Dwyer
authors.affiliation: Chapel Allerton Hospital, Leeds, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.affiliation: Barts and The London School of Medicine and Dentistry, London, UK.
authors.forename: Costantino
authors.initials: C
authors.lastname: Pitzalis
authors.affiliation: University of Newcastle, Newcastle-upon-Tyne, UK.
authors.forename: Wan-Fai
authors.identifier: 0000-0002-5539-388X
authors.initials: WF
authors.lastname: Ng
authors.affiliation: Chapel Allerton Hospital, Leeds, UK.
authors.forename: Colin T
authors.initials: CT
authors.lastname: Pease
authors.affiliation: Great Western Hospital, Swindon, UK.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Price
authors.affiliation: Royal London Hospital (Mile End), London, UK.
authors.forename: Nurhan
authors.initials: N
authors.lastname: Sutcliffe
authors.affiliation: Basildon and Thurrock University Hospital, Essex, UK.
authors.forename: Nagui S T
authors.initials: NST
authors.lastname: Gendi
authors.affiliation: University of Cambridge, Addenbrookes Hospital, Cambridge, UK.
authors.forename: Frances C
authors.initials: FC
authors.lastname: Hall
authors.affiliation: University of Leeds, Leeds, UK.
authors.forename: Sharon P
authors.initials: SP
authors.lastname: Ruddock
authors.affiliation: University of Leeds, Leeds, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Fernandez
authors.affiliation: University of Leeds, Leeds, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Reynolds
authors.affiliation: University of Leeds, Leeds, UK.
authors.forename: Claire T
authors.initials: CT
authors.lastname: Hulme
authors.affiliation: University of Sussex, Brighton, UK.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Davies
authors.affiliation: NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton, Southampton, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Edwards
authors.affiliation: University of Nottingham and Circle Nottingham, Nottingham NHS Treatment Centre, Nottingham, UK.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Lanyon
authors.affiliation: Aintree University Hospital, Liverpool, UK.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Moots
authors.affiliation: King George Hospital, Barking Havering and Redbridge University Hospitals NHS Trust, Essex, UK.
authors.forename: Euthalia
authors.initials: E
authors.lastname: Roussou
authors.affiliation: University College London Hospital, London, UK.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Giles
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Linda D
authors.initials: LD
authors.lastname: Sharples
authors.affiliation: Barts and The London School of Medicine and Dentistry, London, UK.
authors.forename: Michele
authors.initials: M
authors.lastname: Bombardieri
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000191:economics / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D004311:Double-Blind Method; D005221:Fatigue / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D000071066:Patient Reported Outcome Measures; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D000069283:Rituximab / Q000191:economics / Q000627:therapeutic use*; D012859:Sjogren's Syndrome / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome; D006113:United Kingdom; D064232:Visual Analog Scale; D014987:Xerostomia / Q000188:drug therapy* / Q000209:etiology
chemical_list: D018501:Antirheumatic Agents; D000069283:Rituximab