• Jacques-Eric Gottenberg, Jacques Morel, Elodie Perrodeau, Thomas Bardin, Bernard Combe, Maxime Dougados, Rene-Marc Flipo, Alain Saraux, Thierry Schaeverbeke, Jean Sibilia, Martin Soubrier, Olivier Vittecoq, Gabriel Baron, Arnaud Constantin, Philippe Ravaud, Xavier Mariette, and French Society of Rheumatology and the investigators participating in AIR, ORA, and REGATE registries.
• 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.
• BMJ. 2019 Jan 24; 364: l67.

ObjectiveTo compare the effectiveness and safety of three non-tumour necrosis factor (TNF) α inhibitors (rituximab, abatacept, and tocilizumab) in the treatment of rheumatoid arthritis.DesignPopulation based prospective study.Setting53 university and 54 non-university clinical centres in France.Participants3162 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.InterventionInitiation of intravenous rituximab, abatacept, or tocilizumab for rheumatoid arthritis.Main Outcome MeasureThe 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.ResultsAverage 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.ConclusionAmong 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.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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