title: Survival on treatment with second-line biologic therapy: a cohort study comparing cycling and swap strategies.
abstract: OBJECTIVE
  The aim of this study was to evaluate the survival on treatment with second-line biologic therapy in RA patient non-responders to TNF inhibitors (TNFis) by comparing treatments with a second anti-TNF (cycling strategy) or with agents with a different mechanism of action (MoA; swap strategy).
  
  
  METHODS
  RA patients treated with biologics since 1999 who stopped a first-line TNFi and started a second-line biotherapy were included in this cohort study. After adjusting for propensity scores, drug retention rates were calculated using the Kaplan-Meier method. The log-rank test was used to compare survival curves and the Cox regression model was used to compare risk for discontinuation between the two groups.
  
  
  RESULTS
  Two hundred and one patients discontinued the first TNFi, switching to a second anti-TNF [n = 119 (59.2%)] or to abatacept [n = 26 (31.7%)], rituximab [n = 40 (48.8%)] or tocilizumab [n = 15 (18.3%)]. Drug survival was significantly higher in the swap group than in the cycling group (P < 0.0001). After adjustment for propensity scores, probability of treatment retention in the swap group was significantly higher (hazard ratio = 2.258, 95% CI 1.507, 3.385), even after stratification according to the reason for the first TNFi discontinuation (P = 0.005). No significant differences emerged when comparing the retention rates of different MoAs (P = 0.51) in the swap group.
  
  
  CONCLUSIONS
  In the clinical practice setting, the best option for managing TNFi non-responders seems to be swapping to a different MoA, with no differences between abatacept, rituximab and tocilizumab, irrespective of the reason for first TNFi discontinuation.
authors.affiliation: Department of Rheumatology, Gaetano Pini Institute and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. enniofavalli@me.com.
authors.forename: Ennio Giulio
authors.initials: EG
authors.lastname: Favalli
authors.affiliation: Department of Rheumatology, Gaetano Pini Institute and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.Department of Rheumatology, Gaetano Pini Institute and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Biggioggero
authors.affiliation: Department of Rheumatology, Gaetano Pini Institute and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Marchesoni
authors.affiliation: Department of Rheumatology, Gaetano Pini Institute and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.Department of Rheumatology, Gaetano Pini Institute and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Meroni
mesh_terms: D000069594:Abatacept; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001688:Biological Products / Q000627:therapeutic use*; D001691:Biological Therapy / Q000379:methods*; D015331:Cohort Studies; D057915:Drug Substitution / Q000379:methods*; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D012720:Severity of Illness Index; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D001688:Biological Products; D018796:Immunoconjugates; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab; D000069594:Abatacept; C502936:tocilizumab
keywords: anti-TNF; biologic agents; cycling; drug survival; mechanism of action; rheumatoid arthritis; swap; treatment