Survival on treatment with second-line biologic therapy: a cohort study comparing cycling and swap strategies

Rheumatology (Oxford). 2014 Sep;53(9):1664-8. doi: 10.1093/rheumatology/keu158. Epub 2014 Apr 12.

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.

Conclusion: 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.

Keywords: anti-TNF; biologic agents; cycling; drug survival; mechanism of action; rheumatoid arthritis; swap; treatment.

Publication types

  • Comparative Study

MeSH terms

  • Abatacept
  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Biological Products / therapeutic use*
  • Biological Therapy / methods*
  • Cohort Studies
  • Drug Substitution / methods*
  • Female
  • Humans
  • Immunoconjugates / therapeutic use
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Rituximab
  • Severity of Illness Index
  • Treatment Failure
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents
  • Biological Products
  • Immunoconjugates
  • Tumor Necrosis Factor-alpha
  • Rituximab
  • Abatacept
  • tocilizumab