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Original Investigation
September 20, 2016

Non–TNF-Targeted Biologic vs a Second Anti-TNF Drug to Treat Rheumatoid Arthritis in Patients With Insufficient Response to a First Anti-TNF DrugA Randomized Clinical Trial

Author Affiliations
  • 1Department of Rheumatology, National Reference Center for Systemic Autoimmune Diseases, Strasbourg University Hospital, Université de Strasbourg, Strasbourg, France
  • 2Department of Rheumatology, Centre Hospitalier Princesse Grâce, Monaco
  • 3Department of Rheumatology, Rennes University Hospital, Rennes, France
  • 4Department of Rheumatology, Centre Hospitalier de Cahors, Cahors, France
  • 5Department of Rheumatology, Nantes University Hospital, Nantes, France
  • 6Department of Rheumatology, Besançon University Hospital, Besançon, France
  • 7Department of Rheumatology, Nice University Hospital, Nice, France
  • 8Department of Rheumatology, Clermont-Ferrand University Hospital, Clermont-Ferrand, France
  • 9Department of Rheumatology, Bordeaux University Hospital, Bordeaux, France
  • 10Department of Rheumatology, Hôpital La Pitié Salpétrière, Paris, France
  • 11Department of Rheumatology, Toulouse University Hospital, Toulouse, France
  • 12Department of Rheumatology, Hôpital Kremlin Bicêtre, Kremlin Bicêtre, France
  • 13Department of Rheumatology, Montpellier University Hospital, Montpellier, France
  • 14Department of Rheumatology, Grenoble University Hospital, Grenoble, France
  • 15Department of Rheumatology, Centre Hospitalier de La Roche Sur Yon, La Roche Sur Yon, France
  • 16Department of Rheumatology, Reims University Hospital, Reims, France
  • 17Department of Rheumatology, Centre Hospitalier d’Orléans, Orléans, France
  • 18Department of Rheumatology, Hôpital Lariboisière, Paris, France
  • 19Department of Rheumatology, Saint-Etienne University Hospital, Saint-Etienne, France
  • 20Department of Rheumatology, Limoges University Hospital, Limoges, France
  • 21Department of Rheumatology, Caen University Hospital, Caen France
  • 22Department of Rheumatology, Hôpital Saint-Antoine, Paris, France
  • 23Department of Rheumatology, Hôpital Bichat, Paris, France
  • 24Department of Rheumatology, Poitiers University Hospital, Poitiers, France
  • 25Department of Rheumatology, Marseille University Hospital, Marseille, France
  • 26Department of Rheumatology, Hôpital La Croix Saint Simon, Paris, France
  • 27Department of Rheumatology, Centre Hospitalier du Havre, Le Havre, France
  • 28Department of Rheumatology, Nancy University Hospital, Nancy, France
  • 29Department of Rheumatology, Rouen University Hospital, Rouen, France
  • 30Department of Rheumatology, Brest University Hospital, Brest, France
  • 31Department of Internal Medicine, Institut Montsouris, Paris, France
  • 32Department of Rheumatology, Centre Hospitalier de Cannes, Cannes, France
  • 33Department of Rheumatology, Hôpital Mondor, Créteil, France
  • 34Department of Rheumatology, Centre Hospitalier de Mulhouse, Mulhouse, France
  • 35Department of Rheumatology, Centre Hospitalier du Mans, Le Mans, France
  • 36Department of Rheumatology, Hôpital Ambroise Paré, Paris, France
  • 37Department of Internal Medicine, Hôpital Saint-Antoine, Paris, France
  • 38Department of Rheumatology, Centre Hospitalier de Belfort, Belfort, France
  • 39Department of Direction de la recherche clinique et de l’innovation, Strasbourg University Hospital, Strasbourg, France
  • 40Department of Immunology, Hôpital Necker, Paris, France
  • 41Department of Epidemiology and Biostatistics, Hotel Dieu, Paris, France
JAMA. 2016;316(11):1172-1180. doi:10.1001/jama.2016.13512

Importance  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.

Design, Setting, and Participants  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.

Interventions  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.

Main Outcomes and Measures  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 and Relevance  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.

Trial Registration  clinicaltrials.gov Identifier: NCT01000441