title: Non-TNF-Targeted Biologic vs a Second Anti-TNF Drug to Treat Rheumatoid Arthritis in Patients With Insufficient Response to a First Anti-TNF Drug: A Randomized Clinical Trial.
abstract: OBJECTIVE
  One-third of patients with rheumatoid arthritis show inadequate response to tumor necrosis factor α (TNF-α) inhibitors; little guidance on choosing the next treatment exists.
  
  
  OBJECTIVE
  To compare the efficacy of a non-TNF-targeted biologic (non-TNF) vs a second anti-TNF drug for patients with insufficient response to a TNF inhibitor.
  
  
  METHODS
  A total of 300 patients (conducted between 2009-2012) with rheumatoid arthritis, with persistent disease activity (disease activity score in 28 joints-erythrocyte sedimentation rate [DAS28-ESR]  ≥ 3.2 [range, 0-9.3]) and an insufficient response to anti-TNF therapy were included in a 52-week multicenter, pragmatic, open-label randomized clinical trial. The final follow-up date was in August 2013.
  
  
  METHODS
  Patients were randomly assigned (1:1) to receive a non-TNF-targeted biologic agent or an anti-TNF that differed from their previous treatment. The choice of the biologic prescribed within each randomized group was left to the treating clinician.
  
  
  METHODS
  The primary outcome was the proportion of patients with good or moderate response according to the European League Against Rheumatism (EULAR) scale at week 24. Secondary outcomes included the EULAR response at weeks 12 and 52; at weeks 12, 24, and 52; DAS28ESR, low disease activity (DAS28 ≤3.2), remission (DAS28 ≤2.6); serious adverse events; and serious infections.
  
  
  RESULTS
  Of the 300 randomized patients (243 [83.2%] women; mean [SD] age, 57.1 [12.2] years; baseline DAS28-ESR, 5.1 [1.1]), 269 (89.7%) completed the study. At week 24, 101 of 146 patients (69%) in the non-TNF group and 76 (52%) in the second anti-TNF group achieved a good or moderate EULAR response (OR, 2.06; 95% CI, 1.27-3.37; P = .004, with imputation of missing data; absolute difference, 17.2%; 95% CI, 6.2% to 28.2%). The DAS28-ESR was lower in the non-TNF group than in the second anti-TNF group (mean difference adjusted for baseline differences, -0.43; 95% CI, -0.72 to -0.14; P = .004). At weeks 24 and 52, more patients in the non-TNF group vs the second anti-TNF group showed low disease activity (45% vs 28% at week 24; OR, 2.09; 95% CI, 1.27 to 3.43; P = .004 and 41% vs 23% at week 52; OR, 2.26; 95% CI, 1.33 to 3.86; P = .003).
  
  
  CONCLUSIONS
  Among patients with rheumatoid arthritis previously treated with anti-TNF drugs but with inadequate primary response, a non-TNF biologic agent was more effective in achieving a good or moderate disease activity response at 24 weeks than was the second anti-TNF medication.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01000441.
authors.affiliation: Department of Rheumatology, National Reference Center for Systemic Autoimmune Diseases, Strasbourg University Hospital, Université de Strasbourg, Strasbourg, France.
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authors.affiliation: Department of Rheumatology, Rennes University Hospital, Rennes, France.
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authors.affiliation: Department of Rheumatology, Besançon University Hospital, Besançon, France.
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authors.affiliation: Department of Rheumatology, Nice University Hospital, Nice, France.
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authors.affiliation: Department of Rheumatology, Bordeaux University Hospital, Bordeaux, France.
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authors.affiliation: Department of Rheumatology, Montpellier University Hospital, Montpellier, France.
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authors.affiliation: Department of Rheumatology, Grenoble University Hospital, Grenoble, France.
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authors.affiliation: Department of Rheumatology, Centre Hospitalier d'Orléans, Orléans, France.
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authors.affiliation: Department of Rheumatology, Hôpital Lariboisière, Paris, France.
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authors.affiliation: Department of Rheumatology, Saint-Etienne University Hospital, Saint-Etienne, France.
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authors.affiliation: Department of Rheumatology, Limoges University Hospital, Limoges, France.
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authors.affiliation: Department of Rheumatology, Caen University Hospital, Caen France.
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