Similar Rates of Death, Serious Infections, Cancers, Major Cardiovascular Events in Patients Treated with Abatacept, Rituximab and Tocilizumab: Long-Term Registry Data in 4498 Patients with Rheumatoid Arthritis

Jacques-Eric Gottenberg¹, Jacques Morel^2,3, Arnaud Constantin⁴, Thomas Bardin⁵, Alain Cantagrel^6,7, Bernard Combe⁸, Maxime Dougados^9,10, Rene-Marc Flipo¹¹, Alain Saraux¹², Thierry Schaeverbeke¹³, Jean Sibilia¹⁴, Martin Soubrier¹⁵, Olivier Vittecoq¹⁶, Elodie Perrodeau¹⁷, Philippe Ravaud¹⁸, Xavier Mariette¹⁹ 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, ³Immuno-Rheumatology, University Hospital of Lapeyronie, University Montpellier 1, Montpellier, France, ⁴Rheumatology, CHU Purpan - Hopital Pierre-Paul Riquet, Toulouse, France, ⁵Service de Rhumatologie. Centre Viggo Petersen. Hôpital Lariboisière, Paris, France, ⁶Rheumatology, INSERM CNRS UMR 1043, Paul Sabatier University Toulouse, Purpan Teaching Hospital, Toulouse, France, ⁷Rheumatology, Purpan University Hospital, Toulouse Cedex 9, France, ⁸Département Rhumatologie, Hôpital Lapeyronie, Montpellier, France, ⁹Rheumatology, Paris Descartes University, Paris, France, ¹⁰René Descartes University and Hôpital Cochin, Paris, France, ¹¹Rheumatology, Hopital R Salengro CHRU, Lille, France, ¹²Rheumatology, Brest University Hospital, Brest, France, ¹³Rheumatology, CHU Bordeaux, Bordeaux, France, ¹⁴Department of Rheumatology, Strasbourg University Hospital, Strasbourg, France, ¹⁵Rheumatology, Department of Rheumatology, CHU Gabriel Montpied, Clermont-Ferrand, France, ¹⁶Rheumatology, Rouen University Hospital &INSERM U905, Rouen, France, ¹⁷Epidemiology, Hopital Hotel Dieu, Paris Descartes University, Paris, France, ¹⁸Epidemiology, Hotel Dieu, PARIS, France, ¹⁹Rheumatology, Rheumatology department, Bicetre Hospital, Paris-Sud University, Le Kremlin Bicetre, France

Meeting: ACR/ARHP Annual Meeting 2016

Date of first publication: September 28, 2016

Keywords: Abatacept, registries, Rituximab, safety and tocilizumab

Session Information

Date: Tuesday, November 15, 2016

Title: Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy - Poster III

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Assessment of safety in randomized controlled trials is limited by trial durations, and selection of patients with few or now comorbidities. Such limitations can be overcome by long term registry studies. We aimed to compare the safety of abatacept, rituximab and tocilizumab 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 [MACEs], and cancer) were validated by chart review by three experts. A serious infection was defined as an infection occurring during treatment with abatacept or tocilizumab, during the three months after withdrawal, or during the 12 months after a rituximab infusion and requiring hospitalization and/or intravenous antibiotics and/or resulting in death. MACEs were defined as death of cardiovascular origin, stroke, or myocardial infarction. MACEs and cancers were considered in the analysis regardless of their time of occurrence, even after registry drug discontinuation. A propensity-score approach was used to adjust the comparison between drugs.

Results: Among the 4498 enrolled patients (median disease duration: 11 [5-18] years; history of cancer: 8.9% of patients; previous serious or recurrent infection: 27.3%), 3507 had a follow-up at 24 months for a total follow-up of 18898 patient-years (rituximab, 10545; abatacept, 4912; and tocilizumab, 3441). At month 24, serious infections occurred in 5.2, 4.6, and 4.9/100 patient/years in patients treated with rituximab, abatacept, and tocilizumab, respectively (abatacept versus rituximab: IRR of 0.79 [0.49; 1.27], p= 0.33; tocilizumab versus rituximab: IRR of 0.93 [0.55; 1.57], p= 0.79; abatacept versus tocilizumab: IRR of 0.85 [0.47; 1.54], p= 0.59). At month 24, MACEs occurred in 0.56, 0.58 and 0.44/100 patient-years in patients treated with rituximab, abatacept, and tocilizumab, respectively (abatacept versus rituximab: IRR of 1.07 [0.54; 2.13], p= 0.84; tocilizumab versus rituximab: IRR of 0.81 [0.30; 2.17], p= 0.67; abatacept versus tocilizumab: IRR of 1.33 [0.47; 3.75], p= 0.59). At month 24, cancers occurred in 1.2, 1.4 and 1.1/100 patient-years in patients treated with rituximab, abatacept, and tocilizumab, respectively (abatacept versus rituximab: IRR of 0.80 [0.41; 1.56], p= 0.51; tocilizumab versus rituximab: IRR of 0.94 [0.43; 2.04], p= 0.87; abatacept versus tocilizumab: IRR of 0.85 [0.39; 1.88], p= 0.69). At month 24, deaths occurred in 1.3, 1.6 and 0.3/100 patient-years in patients treated with rituximab, abatacept, and tocilizumab, respectively (abatacept versus rituximab: IRR of 1.83 [0.87; 3.84], p= 0.11; tocilizumab versus rituximab: IRR of 0.59 [0.18; 2.01], p= 0.40; abatacept versus tocilizumab: IRR of 3.08 [0.78; 12.23], p= 0.11).

Conclusion: In patients with longstanding RA and comorbidities treated in common practice, long term safety seems similar in patients treated with abatacept, rituximab or tocilizumab.

Disclosure: J. E. Gottenberg, Abbvie, BMS, Gsk, Janssen, Lilly, MSD, Pfizer, Roche, UCB, 5; J. Morel, None; A. Constantin, None; T. Bardin, None; A. 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 A, Combe B, Dougados M, Flipo RM, Saraux A, Schaeverbeke T, Sibilia J, Soubrier M, Vittecoq O, Perrodeau E, Ravaud P, Mariette X. Similar Rates of Death, Serious Infections, Cancers, Major Cardiovascular Events in Patients Treated with Abatacept, Rituximab and Tocilizumab: Long-Term Registry Data in 4498 Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/similar-rates-of-death-serious-infections-cancers-major-cardiovascular-events-in-patients-treated-with-abatacept-rituximab-and-tocilizumab-long-term-registry-data-in-4498-patients-with-rheumatoid/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/similar-rates-of-death-serious-infections-cancers-major-cardiovascular-events-in-patients-treated-with-abatacept-rituximab-and-tocilizumab-long-term-registry-data-in-4498-patients-with-rheumatoid/