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JAMA. 2016 Sep 20;316(11):1172-1180. doi: 10.1001/jama.2016.13512.

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.

Author information

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

Abstract

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.

PMID:
27654603
DOI:
10.1001/jama.2016.13512

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