Long-Term Registry Data in 4498 Patients with Rheumatoid Arthritis Indicate a Similar Safety but a Different Drug Retention Between Abatacept, Rituximab and Tocilizumab

Jacques-Eric Gottenberg¹, Jacques Morel², Arnaud Constantin³, Thomas Bardin⁴, Alain G. Cantagrel⁵, Bernard Combe⁶, Maxime Dougados⁷, Rene-Marc Flipo⁸, Alain Saraux⁹, Thierry Schaeverbeke¹⁰, Jean Sibilia¹¹, Martin Soubrier¹², Olivier Vittecoq^13,14, Elodie Perrodeau¹⁵, Philippe Ravaud¹⁶, Xavier Mariette¹⁷ and on behalf of the French Society of Rheumatology and of all the investigators participating to the AIR, ORA and REGATE registries, ¹Department of Rheumatology, Strasbourg University Hospital, Strasbourg, France, ²Rheumatology, Department of Rheumatology, Montpellier University Hospital, Montpellier, France, ³Rheumatology, CHU Purpan - Hopital Pierre-Paul Riquet, Toulouse, France, ⁴Clinique de Rhumatologie, Hopital Lariboisiere, Paris Cedex 10, France, ⁵Rheumatology, Centre Hospitalier Universitaire, Toulouse Purpan, Toulouse, France, ⁶Département Rhumatologie, Hôpital Lapeyronie, Montpellier, France, ⁷Rheumatology, Paris Descartes University, Paris, France, ⁸Rheumatology, University Hospital, Lille, France, ⁹Rheumatology, Brest University Hospital, Brest, France, ¹⁰Rheumatology, CHU Bordeaux, Bordeaux, France, ¹¹Department of Rheumatology, Strasbourg University Hospital, Strasbourg, France, ¹²Rheumatology, Department of Rheumatology, CHU Gabriel Montpied, Clermont-Ferrand, France, ¹³Rheumatology, Rouen University Hospital &INSERM U905, Rouen, France, ¹⁴Rheumatology, Rouen University Hospital, Rouen, France, ¹⁵Epidemiology, Hopital Hotel Dieu, Paris Descartes University, Paris, France, ¹⁶Epidemiologist, PARIS, France, ¹⁷Rheumatology, Rheumatology department, Bicetre Hospital, Paris-Sud University, Le Kremlin Bicetre, France

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Abatacept, registries, Rheumatoid arthritis (RA), rituximab and tocilizumab

Session Information

Date: Monday, November 14, 2016

Title: Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy II: Safety and Cost Effectiveness

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose:

Three non-TNF targeted biologics – rituximab, abatacept, and tocilizumab – are widely used, notably in TNF-IR patients. We aimed to compare the efficacy and safety of the drugs in common practice.

Methods:

This was a multicenter open-label observational study of patients with RA according to 1987 American College of Rheumatology criteria who were initiating rituximab, abatacept, or tocilizumab treatment and enrolled in three French Society of Rheumatology prospective registries (AIR for rituximab, ORA for abatacept, and REGATE for tocilizumab). Severe adverse events (death, serious infection, major adverse cardiovascular events, and cancer) were validated by chart review by three experts. The primary outcome was drug retention without failure at month 24. Failure was defined as all-cause death; rituximab, abatacept, or tocilizumab discontinuation; initiation of a new biologic or a combination of conventional DMARDs; or increase in corticosteroid dose greater than 10 mg/day compared to baseline at two successive visits. We used a propensity-score approach to adjust for differences in observed factors that might affect both treatment assignment and outcome.

Results:

In total, 4,498 patients (abatacept: 1,016, rituximab: 1,984, and tocilizumab: 1,498) were enrolled in the registries, with a follow-up of 18,898 patient-years (abatacept: 4,912, rituximab: 10,545, and tocilizumab: 3,441). Among the 4498 enrolled patients (median disease duration: 11 [5-18] years, 83.3% of patients previously treated with a biologic, median number of prior of anti-TNF 2 [1; 3]), 3,507 patients had a follow-up at month 24. At month 24, 64.6% of patients [95% confidence interval (95% CI): 61.1; 68·5] were still receiving rituximab without failure, 40.0% [95% CI: 36·0; 45·0] abatacept, and 61.3% [95% CI; 54·9; 68·8] tocilizumab (Figure 1). Drug retention without failure was significantly greater with rituximab and tocilizumab than abatacept (hazard ratio 2·00 [95% CI: 1·65; 2·43]; p<0·001, and 1·82 [95% CI: 1·37; 2·41], p<0·001, respectively), with no difference between rituximab and tocilizumab. Concordant results were observed in six sensitivity analyses. At month 60, drug retention without failure was significantly greater with rituximab than abatacept (48.1% [95% CI: 44.3; 52.5] and 21.0% [95% CI: 18.1; 24.6], respectively, HR 2.06 [95% CI: 1.78; 2.39]; p<0·001).

At month 24, 513 patients (6.7/100 patient-years) had experienced at least one of the adverse events of specific interest including serious infection, MACE, cancer, or death: 255 in the rituximab registry (7.3/100 patient-years), 116 in the abatacept registry (6.4/100 patient-years), and 142 in the tocilizumab registry (6.0/100 patient/years) (IRR abatacept versus rituximab: 0.79 [0.56;1.12], p=0.19; IRR tocilizumab versus rituximab: 0.87 [0.58;1.32], p=0.52; IRR abatacept versus tocilizumab 0.91 [0.57;1.47], p=0.71).

Conclusion:

Among patients followed up in common practice with long-standing RA, mostly refractory to at least one previous biologic, the effectiveness at two years seems lower for abatacept than rituximab and tocilizumab. Safety of the three drugs seems similar.

Figure 1. Drug survival without failure in RA patients treated with abatacept, rituximab and tocilizumab

Disclosure: J. E. Gottenberg, None; J. Morel, None; A. Constantin, None; T. Bardin, None; A. G. Cantagrel, None; B. Combe, None; M. Dougados, Pfizer, AbbVie, Celgene, Eli Lilly, Novartis, Roche, and Sanofi-Aventis, 5,Pfizer, AbbVie, UCB, Merck, 8; R. M. Flipo, None; A. Saraux, None; T. Schaeverbeke, None; J. Sibilia, None; M. Soubrier, None; O. Vittecoq, None; E. Perrodeau, None; P. Ravaud, None; X. Mariette, None.

To cite this abstract in AMA style:

Gottenberg JE, Morel J, Constantin A, Bardin T, Cantagrel AG, Combe B, Dougados M, Flipo RM, Saraux A, Schaeverbeke T, Sibilia J, Soubrier M, Vittecoq O, Perrodeau E, Ravaud P, Mariette X. Long-Term Registry Data in 4498 Patients with Rheumatoid Arthritis Indicate a Similar Safety but a Different Drug Retention Between Abatacept, Rituximab and Tocilizumab [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/long-term-registry-data-in-4498-patients-with-rheumatoid-arthritis-indicate-a-similar-safety-but-a-different-drug-retention-between-abatacept-rituximab-and-tocilizumab/. Accessed .

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