title: Step-down strategy of spacing TNF-blocker injections for established rheumatoid arthritis in remission: results of the multicentre non-inferiority randomised open-label controlled trial (STRASS: Spacing of TNF-blocker injections in Rheumatoid ArthritiS Study).
abstract: Tumour necrosis factor (TNF)-blocker tapering has been proposed for patients with rheumatoid arthritis (RA) in remission.
  
  
  OBJECTIVE
  The trial aims to compare the effect of progressive spacing of TNF-blocker injections (S-arm) to their maintenance (M-arm) for established patients with RA in remission.
  
  
  METHODS
  The study was an 18-month equivalence trial which included patients receiving etanercept or adalimumab at stable dose for ≥1 year, patients in remission on 28-joint Disease Activity Score (DAS28) for ≥6 months and patients with stable joint damage. Patients were randomised into two arms: maintenance or injections spacing by 50% every 3 months up to complete stop. Spacing was reversed to the previous interval in case of relapse, and eventually reattempted after remission was reachieved. The primary outcome was the standardised difference of DAS28 slopes, based on a linear mixed-effects model (equivalence interval set at ±30%).
  
  
  RESULTS
  64 and 73 patients were included in the S-arm and M-arm, respectively, which was less than planned. In the S-arm, TNF blockers were stopped for 39.1%, only tapered for 35.9% and maintained full dose for 20.3%. The equivalence was not demonstrated with a standardised difference of 19% (95% CI -5% to 46%). Relapse was more common in the S-arm (76.6% vs 46.5%, p=0.0004). However, there was no difference in structural damage progression.
  
  
  CONCLUSIONS
  Tapering was not equivalent to maintenance strategy, resulting in more relapses without impacting structural damage progression. Further studies are needed to identify patients who could benefit from such a strategy associated with substantial cost savings.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00780793; EudraCT identifier: 2007-004483-41.
authors.affiliation: Pierre et Marie Curie University-Paris 6, Sorbonne Universités, GRC-08 (EEMOIS), Paris, France APHP, Rheumatology Department, Pitié Salpêtrière Hospital, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Fautrel
authors.affiliation: Aix-Marseille University, Marseille, France AP-HM, Rheumatology Department, Sainte Marguerite Hospital, Marseille, France.
authors.forename: Thao
authors.initials: T
authors.lastname: Pham
authors.affiliation: APHP, Department of Epidemiology and Clinical Research, Hôpital Bichat, Paris, France INSERM CIC-EC 1425, Paris, France.
authors.forename: Toni
authors.initials: T
authors.lastname: Alfaiate
authors.affiliation: Pierre et Marie Curie University-Paris 6, Sorbonne Universités, GRC-08 (EEMOIS), Paris, France APHP, Rheumatology Department, Pitié Salpêtrière Hospital, Paris, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Gandjbakhch
authors.affiliation: Pierre et Marie Curie University-Paris 6, Sorbonne Universités, GRC-08 (EEMOIS), Paris, France APHP, Rheumatology Department, Pitié Salpêtrière Hospital, Paris, France.
authors.forename: Violaine
authors.initials: V
authors.lastname: Foltz
authors.affiliation: Rheumatology Department, Montpellier 1 University, Lapeyronie Hospital, Montpellier, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Morel
authors.affiliation: Rheumatology Department, Le Mans Hospital, Le Mans, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Dernis
authors.affiliation: Rheumatology Department, Joseph Fourrier University, Sud Hospital, Grenoble, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gaudin
authors.affiliation: Rheumatology Department, Princess Grace Health Centre, Monaco, Monaco.
authors.forename: Olivier
authors.initials: O
authors.lastname: Brocq
authors.affiliation: University of Poitiers, Poitiers, France Rheumatology Department, La Miletrie Hospital, Poitiers, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Solau-Gervais
authors.affiliation: University of Nantes, Nantes, France Rheumatology Department, Hotel-Dieu Hospital, Nantes, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Berthelot
authors.affiliation: Rheumatology Department, Belfort-Montbeliard Health Center, Belfort, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Balblanc
authors.affiliation: Paris Sud University-Paris 11, Le Kremlin Bicêtre, France AP-HP, Rheumatology Department, Bicêtre Hospital, Le Kremlin Bicêtre, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
authors.affiliation: Aix-Marseille University, Marseille, France University Paris Diderot, Sorbonne Paris Cité, UMR 1123, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Tubach
mesh_terms: D000068879:Adalimumab / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy*; D004334:Drug Administration Schedule; D000068800:Etanercept / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D060046:Maintenance Chemotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D011859:Radiography; D012008:Recurrence; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab; D000068800:Etanercept
keywords: Anti-TNF; Rheumatoid Arthritis; Treatment