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Comparative effectiveness of rituximab, abatacept, and tocilizumab in adults with rheumatoid arthritis and inadequate response to TNF inhibitors: prospective cohort study


Gottenberg JE1,2, Morel J3, Perrodeau E4, Bardin T5, Combe B3, Dougados M6, Flipo RM7, Saraux A8, Schaeverbeke T9, Sibilia J10, Soubrier M11, Vittecoq O12, Baron G4, Constantin A13, Ravaud P4, Mariette X14; French Society of Rheumatology and the investigators participating in AIR, ORA, and REGATE registries. BMJ. 2019 Jan 24;364:l67. doi: 10.1136/bmj.l67.

Author Information

1 Department of Rheumatology, 1 avenue Molière, Strasbourg University Hospital, National Centre For Rare Systemic Autoimmune Diseases, 67000 Strasbourg, France jacques-eric.gottenberg@chru-strasbourg.fr.

2 CNRS UPR3572, Immunologie, Immunopathologie et Chimie Thérapeutique, Institut de Biologie Moléculaire et Cellulaire, 15 rue René Descartes, Strasbourg University, 67000 Strasbourg, France.

3 Department of Rheumatology, Montpellier University Hospital, Montpellier, France.

4 Department of Epidemiology and Public Health, Hotel Dieu, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France.

5 Department of Rheumatology, Lariboisière Hospital, Paris, France.

6 Department of Rheumatology, Cochin Hospital, Paris, France.

7 Department of Rheumatology, University Hospital, Lille, France.

8 Department of Rheumatology, University Hospital, Brest, France.

9 Department of Rheumatology, University Hospital, Bordeaux, France.

10 Department of Rheumatology, 1 avenue Molière, Strasbourg University Hospital, National Centre For Rare Systemic Autoimmune Diseases, 67000 Strasbourg, France.

11 Department of Rheumatology, University Hospital, Clermont Ferrand, France.

12 Department of Rheumatology, University Hospital, Rouen, France.

13 Department of Rheumatology, University Hospital, Toulouse, France.

14 Department of Rheumatology, Université Paris Sud, AP-HP, Hôpitaux Universitaires Paris-Sud, Center for Immunology of viral infections and autoimmune diseases (IMVA), INSERM U1184, Le Kremlin Bicêtre, France.



To compare the effectiveness and safety of three non-tumour necrosis factor (TNF) α inhibitors (rituximab, abatacept, and tocilizumab) in the treatment of rheumatoid arthritis.


Population based prospective study.


53 university and 54 non-university clinical centres in France.


3162 adults (>18 years) with rheumatoid arthritis according to 1987 American College of Rheumatology criteria, enrolled in one of the three French Society of Rheumatology registries; who had no severe cardiovascular disease, active or severe infections, or severe immunodeficiency, with follow-up of at least 24 months.


Initiation of intravenous rituximab, abatacept, or tocilizumab for rheumatoid arthritis.


The primary outcome was drug retention without failure at 24 months. Failure was defined as all cause death; discontinuation of rituximab, abatacept, or tocilizumab; initiation of a new biologic or a combination of conventional disease modifying antirheumatic drugs; or increase in corticosteroid dose >10 mg/d compared with baseline at two successive visits. Because of non-proportional hazards, treatment effects are presented as life expectancy difference without failure (LEDwf), which measures the difference between average duration of survival without failure.


Average durations of survival without failure were 19.8 months for rituximab, 15.6 months for abatacept, and 19.1 months for tocilizumab. Average durations were greater with rituximab (LEDwf 4.1, 95% confidence interval 3.1 to 5.2) and tocilizumab (3.5, 2.1 to 5.0) than with abatacept, and uncertainty about tocilizumab compared with rituximab was substantial (-0.7, -1.9 to 0.5). No evidence was found of difference between treatments for mean duration of survival without death, presence of cancer or serious infections, or major adverse cardiovascular events.


Among adults with refractory rheumatoid arthritis followed-up in routine practice, rituximab and tocilizumab were associated with greater improvements in outcomes at two years compared with abatacept.